CDE-1 Affects Chromosome Segregation through Uridylation of CSR-1-Bound siRNAs

Wolfswinkel, Josien C. van; Claycomb, Julie M.; Batista, Pedro J.; Mello, Craig C.; Berezikov, Eugène; Ketting, René F.

doi:10.1016/j.cell.2009.09.012

Cited by 171 publications

(182 citation statements)

References 51 publications

(79 reference statements)

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“…In all cases, positions following the 22nd position showed a strong bias for U in the RNA sequence but not in the corresponding genomic position, suggesting that most of the longer RNAs result from the untemplated 3 ′ uridylation of 22-nt RNAs. These results are consistent with previous studies that detected 3 ′ uridylated versions of 22G RNAs (van Wolfswinkel et al 2009;de Albuquerque et al 2015). Intriguingly, 3…”

Section: G Rnas and Their Derivatives Are Made From Characteristic supporting

confidence: 83%

Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs

Blumenfeld

Jose

2015

RNA

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Small RNAs regulate gene expression and most genes in the worm Caenorhabditis elegans are subject to their regulation. Here, we analyze small RNA data sets and use reproducible features of RNAs present in multiple data sets to discover a new class of small RNAs and to reveal insights into two known classes of small RNAs-22G RNAs and 26G RNAs. We found that reproducibly detected 22-nt RNAs, although are predominantly RNAs with a G at the 5 ′ end, also include RNAs with A, C, or U at the 5 ′ end. These RNAs are synthesized downstream from characteristic sequence motifs on mRNA and have U-tailed derivatives. Analysis of 26G RNAs revealed that they are processed from a blunt end of double-stranded RNAs and that production of one 26G RNA generates a hotspot immediately downstream for production of another. To our surprise, analysis of RNAs shorter than 18 nt revealed a new class of RNAs, which we call NU RNAs (pronounced "new RNAs") because they have a NU bias at the 5 ′ end, where N is any nucleotide. NU RNAs are antisense to genes and originate downstream from U bases on mRNA. Although many genes have complementary NU RNAs, their genome-wide distribution is distinct from that of previously known classes of small RNAs. Our results suggest that current approaches underestimate reproducibly detected RNAs that are shorter than 18 nt, and theoretical considerations suggest that such shorter RNAs could be used for sequence-specific gene regulation in organisms like C. elegans that have small genomes.

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Section: G Rnas and Their Derivatives Are Made From Characteristic supporting

confidence: 83%

Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs

Blumenfeld

Jose

2015

RNA

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“…Zcchc6 is also a homolog of Caenorhabditis elegans CDE-1, which uridylates a subset of siRNAs bound by the Argonaute protein CSR-1, and loss of CDE-1 leads to aberrant chromosomal segregation and dysregulation of CSR-1-bound siRNAs (van Wolfswinkel et al 2009). In spite of these data, this is the first evidence of Zcchc6 uridylating pre-miRNAs and suggests parallel activity with Zcchc11 and a role in the Lin28 pathway.…”

Section: A Related Tutase Zcchc6 Is Functionally Redundant With Zcchcmentioning

confidence: 99%

Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)

Thornton

Chang

Piskounova

et al. 2012

RNA

187

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The pluripotency factor Lin28 recruits a 39 terminal uridylyl transferase (TUTase) to selectively block let-7 microRNA biogenesis in undifferentiated cells. Zcchc11 (TUTase4/TUT4) was previously identified as an enzyme responsible for Lin28-mediated prelet-7 uridylation and control of let-7 expression. Here we investigate the protein and RNA determinants for this interaction. Biochemical dissection and reconstitution assays reveal the TUTase domains necessary and sufficient for Lin28-enhanced prelet-7 uridylation. A single C2H2-type zinc finger domain of Zcchc11 was found to be responsible for the functional interaction with Lin28. We identify Zcchc6 (TUTase7) as an alternative TUTase that functions with Lin28 in vitro, and accordingly, we find Zcchc11 and Zcchc6 redundantly control let-7 biogenesis in embryonic stem cells. Our study indicates that Lin28 uses two different TUTases to control let-7 expression and has important implications for stem cell biology as well as cancer.

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“…Most of these small RNAs start with G and are either 22 nt or 26 nt in length, reminiscent of C. elegans 22G-and 26G-RNAs. C. elegans 22G-RNAs function in chromosome segregation, transposon silencing, and gene regulation (Ambros et al 2003b;Lim et al 2003;Ruby et al 2006;Pak and Fire 2007;Sijen et al 2007;Claycomb et al 2009;Gent et al 2009;Gu et al 2009;van Wolfswinkel et al 2009;Vasale et al 2010;Zhang et al 2011) C. elegans has two classes of 26G-RNAs that regulate gene expression associated with spermatogenesis (Class I) and early zygotic development (Class II) Conine et al 2010;Gent et al 2010;Vasale et al 2010;Zhang et al 2011).…”

Section: Ascaris Endo-sirnas In Gametogenesis and Embryogenesismentioning

confidence: 99%

Deep small RNA sequencing from the nematodeAscarisreveals conservation, functional diversification, and novel developmental profiles

Wang

Czech²,

Crunk³

et al. 2011

Genome Res.

161

189

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Eukaryotic cells express several classes of small RNAs that regulate gene expression and ensure genome maintenance. Endogenous siRNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs) mainly control gene and transposon expression in the germline, while microRNAs (miRNAs) generally function in post-transcriptional gene silencing in both somatic and germline cells. To provide an evolutionary and developmental perspective on small RNA pathways in nematodes, we identified and characterized known and novel small RNA classes through gametogenesis and embryo development in the parasitic nematode Ascaris suum and compared them with known small RNAs of Caenorhabditis elegans. piRNAs, Piwi-clade Argonautes, and other proteins associated with the piRNA pathway have been lost in Ascaris. miRNAs are synthesized immediately after fertilization in utero, before pronuclear fusion, and before the first cleavage of the zygote. This is the earliest expression of small RNAs ever described at a developmental stage long thought to be transcriptionally quiescent. A comparison of the two classes of Ascaris endo-siRNAs, 22G-RNAs and 26G-RNAs, to those in C. elegans, suggests great diversification and plasticity in the use of small RNA pathways during spermatogenesis in different nematodes. Our data reveal conserved characteristics of nematode small RNAs as well as features unique to Ascaris that illustrate significant flexibility in the use of small RNAs pathways, some of which are likely an adaptation to Ascaris' life cycle and parasitism.

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CDE-1 Affects Chromosome Segregation through Uridylation of CSR-1-Bound siRNAs

Cited by 171 publications

References 51 publications

Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs

Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs

Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)

Deep small RNA sequencing from the nematodeAscarisreveals conservation, functional diversification, and novel developmental profiles

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