A Role for Dynein in the Inhibition of Germ Cell Proliferative Fate

Dorsett, Maia; Schedl, Tim

doi:10.1128/mcb.00815-09

Cited by 32 publications

(40 citation statements)

References 61 publications

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“…This speculative model is supported by the two bands observed in our EMSA results using METTL16-myc-DDK (Fig. 3B) and by the oligomerization activity detected for METT-10 in C. elegans (19). Altogether, it will be interesting to complete the biochemical characterization of METTL16, especially if it is a player in N 6 -methyladenosine biology and the epitranscriptome.…”

Section: Discussionsupporting

confidence: 54%

“…The METTL16-MALAT1 ENE+A RNP may contain additional proteins, such as DYNLL1 (19) or those identified in our RNA pulldown experiment: NPM, DHX9, ILF3, or ILF2 (Fig. 2 B-D).…”

Section: Discussionmentioning

confidence: 92%

“…In this regard, studies of two METTL16-related proteins, METT-10 from Caenorhabditis elegans (38% identity) and YbiN from Escherichia coli (31% identity) (14,18,19), are relevant. Both METTL16 (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA

Brown

Kinzig

DeGregorio

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

220

205

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; reviewed by Brenda L. Bass and Eric M. Phizicky)Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a cancer-promoting long noncoding RNA, accumulates in cells by using a 3′-triple-helical RNA stability element for nuclear expression (ENE). The ENE, a stem-loop structure containing a U-rich internal loop, interacts with a downstream A-rich tract (ENE+A) to form a blunt-ended triple helix composed of nine U • A-U triples interrupted by a C • G-C triple and C-G doublet. This unique structure prompted us to explore the possibility of protein binding. Native gel-shift assays revealed a shift in radiolabeled MALAT1 ENE+A RNA upon addition of HEK293T cell lysate. Competitive gel-shift assays suggested that protein binding depends not only on the triple-helical structure but also its nucleotide composition. Selection from the lysate using a biotinylated-RNA probe followed by mass spectrometry identified methyltransferase-like protein 16 (METTL16), a putative RNA methyltransferase, as an interacting protein of the MALAT1 ENE+A. Gel-shift assays confirmed the METTL16-MALAT1 ENE+A interaction in vitro: Binding was observed with recombinant METTL16, but diminished in lysate depleted of METTL16, and a supershift was detected after adding anti-METTL16 antibody. Importantly, RNA immunoprecipitation after in vivo UV cross-linking and an in situ proximity ligation assay for RNA-protein interactions confirmed an association between METTL16 and MALAT1 in cells. METTL16 is an abundant (∼5 × 10 5 molecules per cell) nuclear protein in HeLa cells. Its identification as a triple-stranded RNA binding protein supports the formation of RNA triple helices inside cells and suggests the existence of a class of triple-stranded RNA binding proteins, which may enable the discovery of additional cellular RNA triple helices.RNA binding protein | RNA triple helix | noncoding RNA

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Section: Discussionsupporting

confidence: 54%

“…The METTL16-MALAT1 ENE+A RNP may contain additional proteins, such as DYNLL1 (19) or those identified in our RNA pulldown experiment: NPM, DHX9, ILF3, or ILF2 (Fig. 2 B-D).…”

Section: Discussionmentioning

confidence: 92%

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Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA

Brown

Kinzig

DeGregorio

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

220

205

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“…dlc-1(tm3153) results in a maternal-effect embryonic lethal phenotype. Homozygous dlc-1 (tm3153) mutants produce both sperm and oocytes; however, oocytes in diakinesis have unpaired chromosomes similar to the dlc-1(RNAi) phenotype (Dorsett and Schedl, 2009; Fig. 1D) and result in dead embryos upon fertilization.…”

Section: Methodsmentioning

confidence: 99%

Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells

et al. 2016

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PUF family translational repressors are conserved developmental regulators, but the molecular function provided by the regions flanking the PUF RNA-binding domain is unknown. In C. elegans, the PUF proteins FBF-1 and FBF-2 support germline progenitor maintenance by repressing production of meiotic proteins and use distinct mechanisms to repress their target mRNAs. We identify dynein light chain DLC-1 as an important regulator of FBF-2 function. DLC-1 directly binds to FBF-2 outside of the RNA-binding domain and promotes FBF-2 localization and function. By contrast, DLC-1 does not interact with FBF-1 and does not contribute to FBF-1 activity. Surprisingly, we find that the contribution of DLC-1 to FBF-2 activity is independent of the dynein motor. Our findings suggest that PUF protein localization and activity are mediated by sequences flanking the RNA-binding domain that bind specific molecular partners. Furthermore, these results identify a new role for DLC-1 in posttranscriptional regulation of gene expression.

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“…4H). As DYNLL1 can sometimes bind to imperfect TQT sites, including SQ motifs (23)(24)(25), we mutated all eleven TQTs (green lollipops in Figs. 1A and 4B; see legend to Fig.…”

Section: Asciz Regulates Dynll1 Expression As a Znf Transcriptionmentioning

confidence: 99%

ATM Substrate Chk2-interacting Zn2+ Finger (ASCIZ) Is a Bi-functional Transcriptional Activator and Feedback Sensor in the Regulation of Dynein Light Chain (DYNLL1) Expression

Jurado

Conlan

Baker

et al. 2012

Journal of Biological Chemistry

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Background:The regulation of multi-functional DYNLL1 is poorly understood. Results: ASCIZ activates Dynll1 gene expression and is inhibited by DYNLL1 binding to its transcription activation domain. Conclusion: ASCIZ plays a key role in the auto-regulation of DYNLL1 levels. Significance: This is the first case where a gene product directly inhibits its main transcriptional activator while bound at its own promoter.

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A Role for Dynein in the Inhibition of Germ Cell Proliferative Fate

Cited by 32 publications

References 61 publications

Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA

Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA

Dynein light chain DLC-1 promotes localization and function of the PUF protein FBF-2 in germline progenitor cells

ATM Substrate Chk2-interacting Zn2+ Finger (ASCIZ) Is a Bi-functional Transcriptional Activator and Feedback Sensor in the Regulation of Dynein Light Chain (DYNLL1) Expression

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