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Lynham, J.;  Houry, W.A. Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization. Encyclopedia. Available online: https://encyclopedia.pub/entry/25819 (accessed on 21 December 2024).
Lynham J,  Houry WA. Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization. Encyclopedia. Available at: https://encyclopedia.pub/entry/25819. Accessed December 21, 2024.
Lynham, Jeffrey, Walid A. Houry. "Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization" Encyclopedia, https://encyclopedia.pub/entry/25819 (accessed December 21, 2024).
Lynham, J., & Houry, W.A. (2022, August 03). Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization. In Encyclopedia. https://encyclopedia.pub/entry/25819
Lynham, Jeffrey and Walid A. Houry. "Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization." Encyclopedia. Web. 03 August, 2022.
Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization
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This entry is adapted from the peer-reviewed paper 10.3390/biom12081045

Hsp90 is a ubiquitous molecular chaperone involved in many cell signaling pathways, and its interactions with specific chaperones and cochaperones determines which client proteins to fold. Hsp90 has been shown to be involved in the promotion and maintenance of proper protein complex assembly either alone or in association with other chaperones such as the R2TP chaperone complex. Hsp90-R2TP acts through several mechanisms, such as by controlling the transcription of protein complex subunits, stabilizing protein subcomplexes before their incorporation into the entire complex, and by recruiting adaptors that facilitate complex assembly.

molecular chaperones Hsp90 R2TP

1. Hsp90 Structure and Its Function with R2TP

The Hsp90 molecular chaperone is a central regulator of protein homeostasis in eukaryotes under normal and stressed conditions. Hsp90 is involved in the final stages of client protein folding and maturation. In mammals, there are two cytoplasmic Hsp90 isoforms, Hsp90α and Hsp90β, while in yeast, Hsp82 and Hsc82 are the inducible and constitutively expressed Hsp90 isoforms, respectively [1]. Hsp90 isoforms (referred to here as Hsp90) exist as dynamic homodimers, with each protomer comprised of three domains: an N-terminal domain, the site of ATP binding and hydrolysis [2]; a middle domain, which interacts with Hsp90 substrates; and a C-terminal domain, which forms the Hsp90 dimerization interface [3]. The C-terminal domain also contains a MEEVD motif, which is important for interactions with Hsp90 cochaperones that contain TPR domains. Hsp90 substrates are called clients, and the current set of Hsp90 clients includes steroid hormone receptors, kinases, transcription factors, E3 ubiquitin ligases, and many others that share no common features in terms of sequence, structure, or function [4]. Hsp90-mediated client folding and stabilization is a regulated process that requires the association and release of chaperones and cochaperones. Hsp90 client loading is largely dependent on Hsp70, which binds to nascent or partially folded polypeptides with exposed hydrophobic residues [5][6], and Hop, which functions as an adaptor between Hsp70 and Hsp90 [7].
In addition to stabilizing tertiary structure, Hsp90 and its cochaperones stabilize the quaternary structure of various macromolecular complexes. In 2005, a group identified Tah1 and Pih1 as Hsp90 interactors in yeast [8]. Tah1 and Pih1 form a heterodimer and interact with AAA+ proteins Rvb1 and Rvb2 to form the R2TP chaperone complex that is conserved in higher eukaryotes including humans. Most notably, the R2TP complex is involved in the assembly of L7Ae ribonucleoproteins [9][10][11], RNA polymerases [12], and PIKK complexes [13]. In humans, R2TP associates with RNA polymerase subunit RPB5, WD40 repeat protein WDR92, and the Unconventional Prefoldin Complex (UPC), comprising of URI1, UXT, PDRG1, PFDN2, PFDN6, and ASDURF [14][15][16]. Altogether, these 12 proteins constitute the PAQosome, Particle for Arrangement of Quaternary Structure [17]. The PAQosome is the largest and most intricate chaperone interacting with Hsp90. The R2TP complex is involved in all PAQosome-mediated pathways as the catalytic component, whereas the function of the other subunits is mostly unknown. WDR92 has a specialized role in dynein arm assembly [18], RPB5 likely bridges the interactions between the PAQosome and RNA polymerases, and the UPC may regulate R2TP in response to cell growth and proliferation [19]. Moreover, URI1 mediates nuclear and cytoplasmic shuttling of RNAP subunits, and it has been suggested to do so as part of the PAQosome [20][21]. Thus, PAQosome assembly may occur in the cytoplasm with URI1 facilitating its transport into the nucleus and vice-versa.
Within the PAQosome, RPAP3 and PIH1D1 are proposed to function as scaffolds for Hsp90 and its diverse client proteins. RPAP3 contains an RPAP3_N domain that mediates interactions with substrates enriched with helical-type domains [22]; two TPR domains, whereby TPR2 has high affinity for Hsp90 [23]; an intrinsically disordered region that makes contacts with RUVBL1 [22]; and an RPAP3_C domain that binds to the ATPase side of RUVBL2 [24]. PIH1D1 contains an N-terminal PIH1 domain that binds DpSDD/E motifs on clients [25][26] and a C-terminal CHORD and Sgt1 (CS) domain that binds RPAP3 [24][27]. Although it has been proposed that PIH1D1 binds to and regulates RUVBL2 ATPase activity as a nucleotide exchange factor, a group has shown that, within the R2TP complex, PIH1D1 binds exclusively to RPAP3 and that PIH1D1 has little effect on RUVBL1/2 ATPase activity and nucleotide binding affinity [22]. Interestingly, although a model suggests that PIH1D1 only interacts with RPAP3 within the R2TP complex, it has been identified R2T and R2P complexes in vitro and in cellulo [22]. The significance of these findings in regard to Hsp90 function has yet to be determined.
In yeast, Tah1 is much smaller than RPAP3 and contains two TPR repeats followed by a C-helix and an unstructured region [28][29]. The TPR domain binds the Hsp90 C-terminal MEEVD motif, while the unstructured region binds Pih1. Yeast Pih1 is slightly larger than PIH1D1 and contains an N-terminal PIH1 domain, which also recruits clients with DpSDD/E motifs, and a C-terminal CS domain that binds Tah1 [26][28][30]. The Tah1-Pih1 dimer binds to the Rvb1/2 hexamer DII domains to form the R2TP complex [31][32]. Yeast R2TP forms an open basket that accommodates client proteins and Hsp90.

2. Hsp90- and R2TP-Mediated RNA Polymerase Assembly and Localization

The eukaryotic RNA polymerases, RNAP I, RNAP II, and RNAP III, are multiprotein complexes that synthesize ribosomal, messenger, and transfer RNA, respectively. The three RNA polymerases are structurally related. Within each complex, the two largest subunits form the catalytic core, while the smaller subunits are located on the periphery. They are also related through having five common subunits: RPB5, RPB6, RPB8, RPB10, and RPB12. Large-scale proteomic screens identified Hsp90, R2TP, and prefoldins as RNAP II interactors [14][16][33][34]. RNAP II is assembled in the cytoplasm by Hsp90 and R2TP and then imported into the nucleus through URI1 [12][20]. To further analyze the interactions of RNAP II subunits during assembly, Boulon and colleagues performed triple-SILAC purifications on U2OS cells treated with α-amanitin, a small molecule that binds RPB1 and induces its degradation [12][35]. Their findings revealed the presence of two subcomplexes: RPB1-RPB8 and RPB2-RPB3-RPB10-RPB11-RPB12. In addition, each subcomplex associated with a specific set of assembly factors, such as RPAP2, GPN2, GPN3, and GrinL1A. RPB1-RPB8 also associated with R2TP/Prefoldin components RPAP3, PFDN2, and UXT [12].
RPB1 is the largest subunit in RNAP II and interacts with many RNAP II subunits and assembly factors. Coprecipitation and yeast two-hybrid experiments showed that Hsp90 interacts with RPB1 and with the TPR2 domain on RPAP3 [12]. RPB1 interacts with RPAP3 outside of the TPR2 domain [12], implying that RPAP3 stabilizes RPB1 by tethering the interaction between Hsp90 and RPB1. Indeed, long-term RPAP3 depletion in U2OS cells resulted in RPB1 loss [12]. Also, RPAP3 depletion resulted in RPB1 cytoplasmic accumulation in mouse intestinal epithelium cells and crypt base columnar stem cells [36]. Another study showed that RNAP II assembly in melanoma cells was dependent on RPB1 interacting with URI1 [37], but the role of the prefoldin-like module during RNAP II assembly is uncharacterized.
The depletion of RNAP subunits leads to the accumulation of unstable cytoplasmic RPB1. Boulon and colleagues showed that siRNA-mediated depletion of any RNAP II subunit in U2OS cells resulted in RPB1 cytoplasmic accumulation [12]. When cells were treated with geldanamycin, there was a significant decrease of RPB1 in RPB2-, RPB3-, RPB5-, RPB8-, RPB10-, RPB11-, and RPB12-depleted cells, but no significant changes of RPB1 in RPB4-, RPB6-, RPB7-, and RPB9-depleted cells [12]. Hsp90 is essential for stabilizing RPB1, however, Hsp90 binding to RPB1 occurred independent of its ATPase activity [12]. To stabilize RPB1, Hsp90 ATPase activity may mediate interactions between RPB1 and RNAP II subunits RPB5, RPB8, and the subcomplex RPB2-RPB3-RPB10-RPB11-RPB12. The remaining RNAP II subunits, RPB4, RPB6, RPB7, and RPB9, are likely nonessential for RPB1 stability and may be integrated at a later stage. Taken together, these findings show that Hsp90 and R2TP stabilize RPB1 by mediating its interactions with other RNAP II subunits.
R2TP may also be involved in RNAP I and RNAP III assembly since RPAP3-based purifications showed interactions with RPA1 and RPC1, the two largest subunits of RNAP I and RNAP III, respectively [12][16]. Depletion of RPA135, the second largest subunit in RNAP I, increased the interaction between RPA1 and RPAP3, demonstrating that RPAP3 preferentially binds to RPA1 when it is unassembled [12].

3. Hsp90- and R2TP-Mediated MRN Complex Stabilization

The MRN complex is involved in sensing, processing, and repairing DNA strand breaks (DSBs). The complex is comprised of the nuclease MRE11, ATPase RAD50, and PIKK scaffold NBS1. During the DNA damage response, the MRN complex binds to DSBs, recruits and activates the PIKKs ATM and ATR, and facilitates DNA repair by homologous recombination and non-homologous end-joining [38][39][40][41][42]. Hypomorphic mutations in MRE11, NBS1, and RAD50 cause ataxia-telangiectasia-like disease [43], Nijmegen breakage syndrome [44], and Nijmegen breakage syndrome-like disorder [45], respectively. Both ataxia-telangiectasia-like disease and Nijmegen breakage syndrome are characterized by genomic instability, hypersensitivity to radiation, and increased susceptibility to cancer.
MRE11 is a conserved 70–90 kDa dimeric protein that has endo- and exonuclease activity against single- and double-stranded DNA [46][47][48]. MRE11 stability was shown to be dependent on its interaction with PIH1D1 [49]. PIH1D1 interacts with MRE11 at S558/S561 or S688/S689 when both serines of each site are phosphorylated, with the latter being the major binding site [49]. Cells expressing MRE11 mutated at S688/S689 had reduced levels of stable MRE11 compared to WT cells [49]. In addition, RPE1, U2OS, and HCT116 cells treated with siRNA against PIH1D1 had reduced levels of MRE11 and slightly reduced levels of RAD50 and NBS1 [49].
RAD50 is a 150 kDa protein that contains an ABC-type ATPase domain that binds and unwinds dsDNA termini [50][51]. Hsp90 ATPase activity is essential for RAD50 expression [52]. HO-8910 ovarian cancer cells treated with 17-AAG had significantly reduced levels of RAD50 [52]. Hsp90 is also important for RAD50-mediated BRCA1 recruitment to DSBs. BRCA1, a tumor suppressor protein linked to breast and ovarian cancer, interacts with RAD50 in vitro and in vivo and co-localizes with RAD50, MRE11, and NBS1 in irradiation-induced foci [53]. In MCF7 breast cancer cells, 17-AAG decreased BRCA1 protein levels in a dose- and time-dependent manner and impaired irradiation-induced homologous recombination and non-homologous end joining [54].
NBS1 is an 85 kDa protein containing two BRCT domains that bind pSDpTD motifs on interacting proteins, including repair and checkpoint proteins at DSBs [55][56]. Hsp90α stabilizes NBS1 and ATM, but not MRE11 and RAD50 [57]. Hsp90 also stabilizes the interaction between NBS1 and ATM and is needed for MRN translocation to nuclear foci after irradiation [58]. Upon irradiation-induced ATM activation, ATM phosphorylates both NBS1 and Hsp90α, and pNBS1 dissociates from pHsp90 and translocates to DSBs [57][59]. When PIKKs phosphorylate Hsp90 at Thr 7, Hsp90α also translocates to DSBs [60]. By contrast, another study showed that when ATM phosphorylates Hsp90 at Thr 5 and Thr 7, Hsp90α is not significantly recruited to DSBs [57]. In addition to regulating Hsp90 localization, Hsp90 phosphorylation is essential for MRN stabilization since Cdc7-Dbf4-mediated phosphorylation of S164 on Hsp90 was required for stabilizing the Hsp90-TELO2-MRN complex and resulted in enhanced ATM/ATR signaling [61].

4. Hsp90- and R2TP-Mediated TSC Complex Stabilization

The TSC complex, comprising of tumor-suppressor proteins TSC1, TSC2, and TBC1D7, inhibits the mTORC1 complex, which controls cell growth and proliferation [62]. Loss-of-function mutations in TSC1 or TSC2 have been linked to tuberous sclerosis, a rare genetic disorder that causes tumor growth in multiple organs and neurological symptoms [63]. Within the TSC complex, TSC1 binds and stabilizes both TSC2 and TBC1D7 [64][65][66]. To inactivate mTORC1, TSC2, which contains a GAP domain, catalyzes the conversion of Rheb-GTP to Rheb-GDP [67][68].
TSC1 was reported to be an Hsp90 cochaperone that inhibits Hsp90 ATPase activity [69]. TSC1 enables TSC2 binding to Hsp90, which prevents TSC2 ubiquitin-mediated proteasomal degradation [69]. TSC1 binding to Hsp90 was also important for stability and activity of kinase client proteins such as c-Src, CDK4, and Ulk1, as well as non-kinase client proteins such as glucocorticoid receptor and folliculin [69]. In bladder cancer cells, TSC1 facilitated Hsp90 acetylation at K407/K419, which increased its binding affinity for Hsp90 inhibitor ganetespib [70]. In contrast to bladder cancer cells, however, CAL-72 and PEER cells, which have a complete loss of TSC1 and reduced TSC2 expression, were also sensitized to ganetespib with IC50 values of 22 and 3 nM, respectively [71]. In addition, hepatocellular cancer cell lines SNU-398, SNU-878, and SNU-886, which have a complete loss of TSC2 and normal TSC1 expression, had IC50 values of 9, 14, and 35 nM, respectively [71]. Nevertheless, these findings show that TSC1 and TSC2 influence Hsp90 activity.
The TSC complex may be stabilized through the PAQosome. Co-IP experiments in HeLa cells showed that FLAG-tagged URI1 and RPAP3 interacted with endogenous TSC1 and TSC2 [72]. TAP-MS of each TSC complex subunit demonstrated high confidence interactions with RUVBL1, RUVBL2, RPAP3, PIH1D1, WDR92, and URI1 [72]. A SILAC proteomic analysis using the N-terminal domain of PIH1D1 showed that it associated with all three subunits of the TSC complex [73]. The significance of these interactions is unknown. The PAQosome may act as a loading dock that stabilizes each TSC subunit before combining them into a single complex. Moreover, the PAQosome may scaffold TSC1, to regulate Hsp90 ATPase activity, or it may scaffold TSC2, to facilitate loading onto Hsp90 [69].

5. Axonemal Dynein Arm Assembly

Motile cilia are small microtubule-based organelles required for fluid transport and cell motility in many organisms. In humans, motile cilia are essential for the generation of left-right asymmetry during embryonic development, sperm motility, and the movement of fluid in the respiratory tract, brain ventricular system, and oviducts [74]. Motile cilia contain a 9 + 2 axoneme comprised of nine outer doublet microtubules and a pair of central microtubules. Between each outer doublet, there are several multiprotein complexes, which include the inner dynein arms (IDA) and outer dynein arms (ODA). Dynein is a AAA+ ATPase that mediates microtubule sliding and subsequent ciliary movement [75]. Before being incorporated into the axoneme, dynein arms are preassembled in the cytoplasm [76][77].

5.1. DNAAFs Form Complexes with Hsp90

DNAAFs were discovered through genetic analyses of families with primary ciliary dyskinesia and mutation studies in animals [77][78][79][80][81][82][83][84][85][86][87][88]. Although most of their functions are still being investigated, it is clear that DNAAFs work together with Hsp90 to mediate IDA and ODA assembly [89]. DNAAF2, DNAAF4, DNAAF6, and DNAAF11 have domains that associate with Hsp90, including PIH1, CS, and TPR domains, while DNAAF1, DNAAF3, DNAAF5, and DNAAF7 lack Hsp90 association domains.
In vertebrates, the PIH1 domain is present in at least four proteins: DNAAF2, DNAAF6, PIH1D1, and PIH1D2 [90][91][92]. Each protein has been shown to be involved in ciliary dynein arm assembly [91]. DNAAF2 and DNAAF6 each contain an N-terminal PIH1 domain followed by a CS domain. In mouse testis extracts, DNAAF2 coprecipitated with Hsp70 but not Hsp90 [84], whereas DNAAF6 coprecipitated with both Hsp70 and Hsp90 [90]. In addition, a yeast two-hybrid analysis showed that DNAAF6 interacts with Hsp90, DNAAF2, and DNAAF4 [85].
DNAAF4 contains a C-terminal TPR domain, and a yeast two-hybrid screen showed that it interacts with Hsp70 and Hsp90 C-termini via the EEVD motif that binds TPR domains [93]. These interactions were confirmed through coprecipitation experiments in mouse trachea tissues [86]. In addition, DNAAF4 coprecipitated with DNAAF2 in HEK293 cells [86]. Based on their domains, DNAAF2 and DNAAF4 may form R2TP-like complexes that mediate Hsp90 involvement in dynein arm assembly [26]. Moreover, TTC12 has recently emerged as another dynein arm assembly factor, and it contains a stretch of three TPR domains [94], suggesting that it may also be involved in forming R2TP-like complexes.
DNAAF1 and DNAAF7, which lack Hsp90 binding domains, have been linked to Hsp90. Streptavidin-II/FLAG tandem affinity purification coupled with mass spectrometry (SF-TAP/MS) experiments using HEK293 lysates showed that DNAAF1 associates with several Hsps, including Hsp70 and Hsp90 [95]. Although DNAAF7 lacks an Hsp90 binding domain, endogenous DNAAF7 coprecipitations from P30 mouse testes, P7 mouse oviducts, and primary ciliated HEK293 cells revealed the presence of Hsp90 [96]. Hsp90 may have an indirect interaction with DNAAF7 through FKBP8, an immunophilin belonging to the FK506-binding protein family, thereby forming a DNAAF7-FKBP8-Hsp90 complex. FKBP8 contains a TPR domain that interacts with Hsp90 [97], and it was present in endogenous DNAAF7 coprecipitations from P30 mouse testes and differentiating human tracheal epithelial cultures [96]. There have been no reports linking DNAAF3 and DNAAF5 to Hsp90. Aside from it being essential for dynein arm assembly, little is known about DNAAF3 function, but it may have a role similar to DNAAF1 and DNAAF2 [77]. Coprecipitation experiments using human bronchial epithelial tissues showed that DNAAF5 does not interact with Hsp70 or Hsp90 [78].
DNAAF11 (formerly named LRRC6) is another essential protein for dynein arm assembly [98][99]. HEK293T cells co-expressing DNAAF7 and DNAAF11 and treated with protein synthesis inhibitor cycloheximide for 48 h had 44.4% of its DNAAF11 remaining, while DNAAF11 expressed alone had 7.8% remaining [100], indicating that DNAAF7 is needed to stabilize DNAAF11. DNAAF11 may interact with Hsp90 directly through its CS domain, or indirectly through its interactors DNAAF7 and RUVBL2 [82][87][96][101]. To release client proteins from Hsp90, p23 binding and ATP hydrolysis is required [102]. Thus, DNAAF11 binding to Hsp90 may promote the release of dynein arms from DNAAF7-FKBP8-Hsp90 to other chaperone complexes, including R2TP and R2TP-like complexes [96].

5.2. R2TP and R2TP-like Complexes Are Dynein Arm Assembly Factors

The R2TP complex may be involved in late-stage dynein arm assembly. Similar to DNAAFs, the catalytic components of R2TP, RUVBL1 and RUVBL2, were demonstrated to be involved in dynein arm assembly through mutational analyses in animal models. Inducible deletion of RUVBL1 in mouse oviducts resulted in the absence of outer dynein arms and the appearance of undefined protein clusters [103]. Streptavidin-II/FLAG tandem affinity purification (SF-TAP) using HEK293 cell lysates showed that DNAAF1 interacts with RUVBL1 and RUVBL2, and that the RUVBL1 interaction was reduced with mutant DNAAF1 [95]. RUVBL1 knockdown in hTERT-RPE1 cells showed increased co-localization between intraflagellar transport protein IFT1 and DNAAF1, suggesting that RUVBL1 mediates DNAAF1 transport or localization [95]. In zebrafish, RUVBL1 and RUVBL2 are enriched in cytoplasmic puncta in zebrafish ciliated tissues, and cilia motility is lost in zebrafish with either RUVBL1 or RUVBL2 mutants [101][104]. RUVBL2 interacts with DNAAF11, which has a similar domain composition to DNAAF1 [101]. The RUVBL2-DNAAF11 complex was essential for dynein arm assembly in zebrafish [101]. Altogether, these findings suggest the presence of cytoplasmic R2TP-like complexes that mediate dynein arm assembly.
In a conditional mouse model, loss of RUVBL1 resulted in immotile spermatozoa due to reduced ODA components, DNAI1 and DNAI2 [104]. In mouse testes, RUVBL2 interacted with Hsp90, suggesting that RUVBL2 scaffolds DNAI1 and DNAI2 to Hsp90 [104]. RUVBL1 may also scaffold IDA and ODA components to Hsp90 through the R2TP-like complex R2SP, comprising of RUVBL1, RUVBL2, SPAG1, and PIH1D2 [105]. Both SPAG1 and RPAP3 contain RPAP3_C and TPR domains, while PIH1D1 and PIH1D2 both contain N-terminal PIH1 and C-terminal CS domains. In zebrafish, SPAG1 null mutations resulted in dorsal body curvature and hydrocephalus, indications of primary ciliary dyskinesia [106], while double-null mutations in PIH1D2 and DNAAF2 resulted in abnormal sperm motility [91]. RUVBL2, SPAG1, and PIH1D2 were found to be ubiquitously expressed in all human tissues and had moderate to high enrichment in the testes [105]. The R2SP complex was shown to facilitate the formation of liprin-α2 complexes [105], which are involved in synaptic vesicle release [107]. Interestingly, PIH1 domain-containing proteins DNAAF2 and DNAAF6 were also enriched in the testes, suggesting the presence of multiple R2TP-like complexes [105].
In addition to R2TP and R2TP-like complexes, proper dynein arm assembly requires WDR92 (recently renamed DNAAF10), which is also highly expressed in human testes [108]. In Chlamydomonas, experiments using insertion and truncation mutants showed that WDR92 is needed to stabilize ODA and IDA heavy chains during preassembly [109][110]. Co-IPs using HEK293 cells and in vitro pulldowns showed that WDR92 interacts directly with RPAP3 [109][111], suggesting that a WDR92-R2TP complex is needed for proper dynein arm assembly. In addition, Drosophila WDR92 was shown to interact with CG18472, the closest Drosophila orthologue of human SPAG1 [106][112]. A proteomic analysis also supports a possible interaction between human WDR92 and SPAG1 [72]. These findings suggest the possibility of a WDR92-R2SP complex.
RUVBL1 and RUVBL2 were recently demonstrated to be involved in the synthesis of cytoplasmic cilia, in which the axoneme is exposed to the cytoplasm [113][114]. Cytoplasmic cilia are found in male gametes, including human and Drosophila sperm. While investigating Drosophila spermiogenesis, Fingerhut and colleagues identified a novel RNP granule located at the axoneme distal end, the site of ciliogenesis [114]. The RNP granule contained RUVBL1 and RUVBL2, as well as mRNA that encodes axonemal dynein arms. By localizing translation, dynein arms can be integrated into the axoneme directly from the cytoplasm. RUVBL1 and RUVBL2 were essential for dynein arm integration and subsequent spermatozoa motility. Similar to their involvement with other RNPs, RUVBL1 and RUVBL2 were also essential for RNP granule formation [114].

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Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Jeffrey Lynham
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Walid A. Houry
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Revisions: 3 times (View History)
Update Date: 05 Aug 2022
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