U1 snRNP regulates chromatin retention of noncoding RNAs

Yin, Yafei; Lu, Jiangbo; Zhang, Xuechun; Shao, Wen; Xu, Yanhui; Li, Pan; Hong, Yantao; Zhang, Qiangfeng Cliff; Shen, Xiaohua

doi:10.1101/310433

Cited by 9 publications

(12 citation statements)

References 90 publications

(33 reference statements)

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“…On the other hand, tethering of enhancer-associated transcripts at their site of transcription has been shown to alter local chromatin environment (Lai et al 2013; Li et al 2013; Hsieh et al 2014; Bose et al 2017). Chromatin-bound lncRNAs have been recently shown to be enriched in U1 small nuclear ribonucleoprotein (snRNP) binding, a protein essential for the recognition of nascent RNA 5’ splice site and assembly of the spliceosome (Yin et al 2020). The depletion of U1 snRNP reduced the tethering of lncRNAs to chromatin, suggesting a mechanism by which elncRNA splicing can strengthen enhancer activity (Yin et al 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Chromatin-bound lncRNAs have been recently shown to be enriched in U1 small nuclear ribonucleoprotein (snRNP) binding, a protein essential for the recognition of nascent RNA 5’ splice site and assembly of the spliceosome (Yin et al 2020). The depletion of U1 snRNP reduced the tethering of lncRNAs to chromatin, suggesting a mechanism by which elncRNA splicing can strengthen enhancer activity (Yin et al 2020).…”

Section: Discussionmentioning

confidence: 99%

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The activity of human enhancers is modulated by the splicing of their associated lncRNAs

Marques

2020

Preprint

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1Pervasive enhancer transcription is at the origin of more than half of all long 2 noncoding RNAs in humans. Transcription of enhancer-associated long 3 noncoding RNAs (elncRNA) contribute to their cognate enhancer activity and 4 gene expression regulation in cis. Recently, splicing of elncRNAs was shown 5 to be associated with elevated enhancer activity. However, whether splicing of 6 elncRNA transcripts is a mere consequence of accessibility at highly active 7 enhancers or if elncRNA splicing directly impacts enhancer function, remains 8 unanswered. 9We analysed genetically driven changes in elncRNA expression, in humans, to 10 address this outstanding question. We showed that splicing related motifs 11 within multi-exonic elncRNAs evolved under selective constraints during human 12 evolution, suggesting the processing of these transcripts is unlikely to have 13 resulted from transcription across spurious splice sites. Using a genome-wide 14 and unbiased approach, we used nucleotide variants as independent genetic 15 factors to directly assess the causal relationship that underpin elncRNA splicing 16and their cognate enhancer activity. We found that the splicing of most 17 elncRNAs is associated with changes in chromatin signatures at cognate 18 enhancers and target mRNA expression. 19We conclude that efficient and conserved processing of enhancer-associated 20 elncRNAs contributes to enhancer activity. 21 22

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The activity of human enhancers is modulated by the splicing of their associated lncRNAs

Marques

2020

Preprint

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“…While, the above mentioned examples have all been revealed on a case‐by‐case basis, more global approaches have also been taken to identify common motifs involved in nuclear retention of transcripts (Carlevaro‐Fita et al, ; Gudenas & Wang, ; Lubelsky & Ulitsky, ; Shukla et al, ; Yin et al, ; Zuckerman & Ulitsky, ). Recent high‐throughput approaches employed a systematic design using tiled overlapping sequences to screen for cis ‐acting motifs (Lubelsky & Ulitsky, ; Shukla et al, ).…”

Section: Main Bodymentioning

confidence: 99%

“…This motif element, referred to as short interspersed nuclear element (SINE)‐derived nuclear RNA localization (SIRLOIN), was further shown to bind the abundant nuclear protein hnRNPK, consistent with its known preference for C‐rich motifs (Choi et al, ; Lubelsky & Ulitsky, ). The screen from Yin and colleagues (Yin et al, ) more specifically focussed on identifying cis elements involved in RNA association with chromatin. This method, termed RNA element for subcellular localization by sequencing (RELseq), took short sequences of known chromatin‐associated RNAs and fused them to reporters before fractionating and sequencing.…”

Section: Main Bodymentioning

confidence: 99%

“…This notion was supported by a related study, showing that nuclear retention of the MEG3 lncRNA depends on U1 snRNP components (Azam et al, ). Depletion of hnRNPK or U1‐snRNP factors resultingly disturbed the nuclear localization of RNAs containing SIRLOIN motifs or U1 recognition motifs respectively (Azam et al, ; Lubelsky & Ulitsky, ; Yin et al, ). However, fusion of the C‐rich element identified in the MPRNA study was not sufficient to retain a known cytoplasmic RNA in the nucleus (Shukla et al, ).…”

Section: Main Bodymentioning

confidence: 99%

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Nuclear sorting of RNA

Garland

Jensen

2019

WIREs RNA

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The majority of the mammalian genome is transcribed by RNA polymerase II, yielding a vast amount of noncoding RNA (ncRNA) in addition to the standard production of mRNA. The typical nuclear biogenesis of mRNA relies on the tightly controlled coupling of co‐ and post‐transcriptional processing events, which ultimately results in the export of transcripts into the cytoplasm. These processes are subject to surveillance by nuclear RNA decay pathways to prevent the export of aberrant, or otherwise “non‐optimal,” transcripts. However, unlike mRNA, many long ncRNAs are nuclear retained and those that maintain enduring functions must employ precautions to evade decay. Proper sorting and localization of RNA is therefore an essential activity in eukaryotic cells and the formation of ribonucleoprotein complexes during early stages of RNA synthesis is central to deciding such transcript fate. This review details our current understanding of the pathways and factors that direct RNAs towards a particular destiny and how transcripts combat the adverse conditions of the nucleus. This article is categorized under: RNA Export and Localization > Nuclear Export/Import RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

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Long non‐coding RNAs in development and disease: conservation to mechanisms

Tsagakis

Douka

Birds

et al. 2020

The Journal of Pathology

145

118

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Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein-coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the 'dark matter' of our genomes, our understanding of which is extremely limited. Part of this 'dark matter' includes regions that give rise to RNAs that do not code for proteins. A subset of these non-coding RNAs are long non-coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy.No conflicts of interest were declared. What are lncRNAs?LncRNAs are RNAs of >200 nucleotides (nt) in length that are not thought to code for proteins. Although our appreciation and understanding of lncRNA function and importance has exploded in the last decade, the first lncRNAs were discovered in the 1990s: BC200, H19 [1], and Xist [2]. In the post-genomic era, extensive and deep RNA-Seq has revealed the existence of huge numbers of novel RNA transcripts, including lncRNAs. Many of these novel transcripts are low in abundance and so were not previously identified. Several consortia have been responsible for sequencing RNA from a variety of tissues, cell types, organisms, and disease states, and we now have a much more precise view of which RNA transcripts are expressed, and when and where (GENCODE [3], GTEX [4], FANTOM [5]).

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U1 snRNP regulates chromatin retention of noncoding RNAs

Cited by 9 publications

References 90 publications

The activity of human enhancers is modulated by the splicing of their associated lncRNAs

The activity of human enhancers is modulated by the splicing of their associated lncRNAs

Nuclear sorting of RNA

Long non‐coding RNAs in development and disease: conservation to mechanisms

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