Control of mouse U1 snRNA gene expression during in vitro differentiation of mouse embryonic stem cells

Cheng, Ying

doi:10.1093/nar/25.11.2197

Cited by 12 publications

(11 citation statements)

References 47 publications

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“…S8). This is in agreement with previous studies in mice, which show that a reduction in the embryo-specific U1b snRNA level is only detectable in 11 to 19-d-old embryos (Cheng et al 1997). This might reflect that vU1 snRNAs are as stable as the U1 snRNA, which has an estimated half-life of 4-5 d (Sauterer et al 1988).…”

Section: Some Vu1 Snrna Genes Are Differentially Expressedsupporting

confidence: 94%

“…Numerous reports have documented the expression of variant U1 snRNAs during development of mouse, sea urchin, frog, and fly embryos (Forbes et al 1984;Santiago and Marzluff 1989;Lo and Mount 1990;Cheng et al 1997), which differ from their corresponding U1 snRNAs by only a few bases. U1 snRNA is generally constitutively expressed at all stages of development, whereas the U1 snRNA variants appear to be restricted to early embryo development (Lund et al 1985).…”

Section: Some Vu1 Snrna Genes Are Differentially Expressedmentioning

confidence: 99%

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Differentially expressed, variant U1 snRNAs regulate gene expression in human cells

et al. 2012

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Human U1 small nuclear (sn)RNA, required for splicing of pre-mRNA, is encoded by genes on chromosome 1 (1p36). Imperfect copies of these U1 snRNA genes, also located on chromosome 1 (1q12-21), were thought to be pseudogenes. However, many of these “variant” (v)U1 snRNA genes produce fully processed transcripts. Using antisense oligonucleotides to block the activity of a specific vU1 snRNA in HeLa cells, we have identified global transcriptome changes following interrogation of the Affymetrix Human Exon ST 1.0 array. Our results indicate that this vU1 snRNA regulates expression of a subset of target genes at the level of pre-mRNA processing. This is the first indication that variant U1 snRNAs have a biological function in vivo. Furthermore, some vU1 snRNAs are packaged into unique ribonucleoproteins (RNPs), and many vU1 snRNA genes are differentially expressed in human embryonic stem cells (hESCs) and HeLa cells, suggesting developmental control of RNA processing through expression of different sets of vU1 snRNPs.

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Section: Some Vu1 Snrna Genes Are Differentially Expressedsupporting

confidence: 94%

Section: Some Vu1 Snrna Genes Are Differentially Expressedmentioning

confidence: 99%

Differentially expressed, variant U1 snRNAs regulate gene expression in human cells

et al. 2012

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“…For instance in Drosophila several variants are expressed during early embryogenesis, but eventually one variant gradually dominates expression (11,12). Similar expression patterns for snRNA variants were observed in Xenopus (13)(14)(15), mouse (12,16), sea urchin (17,18), and flatworm (19). Comparable findings have been reported for: snRNA U2 in silk moth (20) and…”

Section: Introductionsupporting

confidence: 63%

An alternative spliceosome defined by distinct snRNAs in early zebrafish embryogenesis

Pagano

Dekker

Ensink

et al. 2019

Preprint

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Alternative snRNAs in early zebrafish embryogenesissnRNA, spliceosome, dual translation machinery, embryogenesis 2 1 ABSTRACT 2 Splicing removes intronic RNA sequences are removed from pre-mRNA molecules and 3 enables, by alternative splicing, the generation of multiple unique RNA molecules from a 4 single gene. As such, splicing is an essential part of the whole translation system of a cell. 5 The spliceosome is a ribonucleoprotein complex in which five small nuclear RNAs (snRNAs) 6 are involved; U1, U2, U4, U5, and U6. For each of these snRNAs there are variant gene 7 copies present in a genome. Furthermore, in many eukaryotic species there is an 8 alternative, minor spliceosome that can splice a small number of specific introns. As we 9 previously discovered an embryogenesis-specific ribosomal system in zebrafish early 10 embryogenesis based on variant rRNA and snoRNA expression, we hypothesized that there 11 may also be an embryogenesis-specific spliceosome. An inventory of zebrafish snRNA genes 12 revealed clustered and dispersed loci for all but U2 major snRNAs. For each minor 13 spliceosome snRNA, just one gene locus was found. Since complete snRNA molecules are 14 hard to sequence, we employed a combined PCR-sequencing approach to measure the 15 individual snRNA-variant presence. Analysis of egg and male-adult samples revealed 16 embryogenesis-specific and somatic-specific variants for each major snRNA. These variants 17 have substantial sequence differences, yet none in their mRNA binding sites. Given that 18 many of the sequence differences are found in loop structures indicate possible alternative 19 protein binding. Altogether, with this study we established that the spliceosome is also an 20 element of the embryogenesis-specific translation system in zebrafish. 21 22 23 24 25 26 27 3 28 INTRODUCTION29 Alternative splicing is fundamental for gene regulation and the generation of different 30 transcripts and/or proteins from an individual gene in eukaryotes (1). Splicing is executed by 31 the spliceosome and removes intronic sequences from pre-mRNA during the maturation 32 process in which the exonic sequences eventually form the mRNA (2,3).The spliceosome is a 33 molecular complex formed by hundreds of proteins and five essential small-nuclear RNAs 34 (snRNAs) that are typically located in the nucleus. The size of these small RNA molecules 35 ranges from 118 nucleotides (nt) to 191 nt. As they are uracil rich, they are called U1, U2, 36 U4, U5 and U6 snRNAs. Next to this major spliceosome, a minor (or U12 dependent) 37 spliceosome exists in many eukaryotic species, which is involved in the splicing of a relative 38 small number of specific introns (4). The snRNAs involved in the minor spliceosome are: 39 U11, U12, U4atac, and U6atac, completed by the U5 from the major spliceosome (4).40 As splicing is at the core of the cellular translation system, the sequences of the involved 41 snRNA are highly conserved across species. At the same time, many non-canonical variants 42 and gene copies of the major s...

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“…Quantitation of nascent levels of the different U1 populations in this report suggests that U1/vU1 genes are differentially regulated at the level of transcription during differentiation and cell re-reprogramming. In agreement with this, developmental regulation of mouse vU1 genes (U1b) requires sequences located downstream of the Proximal sequence element (PSE) regulatory element within the vU1 promoter region (22). However, it is also well known that the steady state levels of U1 are vastly different from vU1 levels across the different cell types (100- to 1000-fold) despite the fact that their nascent levels are comparable in some cell types (75).…”

Section: Discussionmentioning

confidence: 79%

Variant U1 snRNAs are implicated in human pluripotent stem cell maintenance and neuromuscular disease

et al. 2016

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The U1 small nuclear (sn)RNA (U1) is a multifunctional ncRNA, known for its pivotal role in pre-mRNA splicing and regulation of RNA 3′ end processing events. We recently demonstrated that a new class of human U1-like snRNAs, the variant (v)U1 snRNAs (vU1s), also participate in pre-mRNA processing events. In this study, we show that several human vU1 genes are specifically upregulated in stem cells and participate in the regulation of cell fate decisions. Significantly, ectopic expression of vU1 genes in human skin fibroblasts leads to increases in levels of key pluripotent stem cell mRNA markers, including NANOG and SOX2. These results reveal an important role for vU1s in the control of key regulatory networks orchestrating the transitions between stem cell maintenance and differentiation. Moreover, vU1 expression varies inversely with U1 expression during differentiation and cell re-programming and this pattern of expression is specifically de-regulated in iPSC-derived motor neurons from Spinal Muscular Atrophy (SMA) type 1 patient's. Accordingly, we suggest that an imbalance in the vU1/U1 ratio, rather than an overall reduction in Uridyl-rich (U)-snRNAs, may contribute to the specific neuromuscular disease phenotype associated with SMA.

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Control of mouse U1 snRNA gene expression during in vitro differentiation of mouse embryonic stem cells

Cited by 12 publications

References 47 publications

Differentially expressed, variant U1 snRNAs regulate gene expression in human cells

Differentially expressed, variant U1 snRNAs regulate gene expression in human cells

An alternative spliceosome defined by distinct snRNAs in early zebrafish embryogenesis

Variant U1 snRNAs are implicated in human pluripotent stem cell maintenance and neuromuscular disease

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