UBL5 is essential for pre‐<scp>mRNA</scp> splicing and sister chromatid cohesion in human cells

Oka, Yasuyoshi; Varmark, Hanne; Vitting-Seerup, Kristoffer; Beli, Petra; Waage, Johannes; Հակոբյան, Աննա; Mistrík, Martin; Choudhary, Chunaram; Rohde, Mikkel; Bekker‐Jensen, Simon; Mailand, Niels

doi:10.15252/embr.201438679

Cited by 44 publications

(65 citation statements)

References 26 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned above, sororin is a cohesin-associated factor and defects in sororin splicing strongly impair sister chromatid cohesion (Oka et al, 2014;Sundaramoorthy et al, 2014;van der Lelij et al, 2014;Watrin et al, 2014), as is also the case for cactin depletion. To investigate to what extent sororin mis-splicing contributed to the cohesion defects induced by cactin depletion, we depleted cactin in HeLa cells infected with lentiviruses carrying an intron-less and UTR-less sororin cDNA under the control of a doxycycline (dox)-inducible promoter ( pL-Sor).…”

Section: -E)mentioning

confidence: 77%

“…Cactin promotes splicing of sororin pre-mRNA While searching for mis-spliced transcripts that could account for the cellular defects arising upon cactin depletion, the cohesin accessory factor sororin (CDCA5 in Table S1) caught our attention because erroneous splicing of its pre-mRNA was previously reported to cause premature separation of sister chromatids (Oka et al, 2014;Sundaramoorthy et al, 2014;van der Lelij et al, 2014;Watrin et al, 2014), a major phenotype induced by cactin depletion. In our RNA-seq data, reads corresponding to sororin intron 1 were over-represented in cactin-depleted samples as compared with control samples, as well as with sororin introns 2-5 both in cactindepleted and control samples (Fig.…”

Section: -E)mentioning

confidence: 99%

“…Thus, cactin is essential for splicing of sororin pre-mRNA and cactin depletion acutely affects splicing of intron 1. Retention of sororin intron 1 is expected to deplete functional sororin proteins in cells either resulting from a failure in mRNA export from the nucleus or, if the aberrant mRNA is exported to the cytoplasm, from the introduction of a premature stop codon that would allow translation of a truncated protein of 117 amino acids instead of 467 (Oka et al, 2014;Sundaramoorthy et al, 2014;van der Lelij et al, 2014;Watrin et al, 2014). Indeed, western blot analysis revealed that the levels of full-length sororin were approximately halved in cactin-depleted samples when compared with control samples (Fig.…”

Section: -E)mentioning

confidence: 99%

See 2 more Smart Citations

Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion

Zanini

Soneson

Lorenzi

et al. 2017

Journal of Cell Science

View full text Add to dashboard Cite

Cactins constitute a family of eukaryotic proteins broadly conserved from yeast to human and required for fundamental processes such as cell proliferation, genome stability maintenance, organismal development and immune response. Cactin proteins have been found to associate with the spliceosome in several model organisms, nevertheless their molecular functions await elucidation. Here we show that depletion of human cactin leads to premature sister chromatid separation, genome instability and cell proliferation arrest. Moreover, cactin is essential for efficient splicing of thousands of pre-mRNAs, and incomplete splicing of the pre-mRNA of sororin (also known as CDCA5), a cohesin-associated factor, is largely responsible for the aberrant chromatid separation in cactin-depleted cells. Lastly, cactin physically and functionally interacts with the spliceosome-associated factors DHX8 and SRRM2. We propose that cellular complexes comprising cactin, DHX8 and SRRM2 sustain precise chromosome segregation, genome stability and cell proliferation by allowing faithful splicing of specific pre-mRNAs. Our data point to novel pathways of gene expression regulation dependent on cactin, and provide an explanation for the pleiotropic dysfunctions deriving from cactin inactivation in distant eukaryotes.

show abstract

Section: -E)mentioning

confidence: 77%

Section: -E)mentioning

confidence: 99%

Section: -E)mentioning

confidence: 99%

See 1 more Smart Citation

Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion

Zanini

Soneson

Lorenzi

et al. 2017

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…(C) Quantitative RT-PCR showing accumulation of long and short GFP transcripts in the indicated genotypes. Stably expressed At5g60390 was used for normalization (Wang et al 2014). acetylation, methylation, and phosphorylation, ubiquitination is increasingly recognized for its role in regulating the spliceosomal cycle (Bellare et al 2008;Song et al 2010;Mishra et al 2011;Korneta et al 2012;Ammon et al 2014;Chen and Moore 2014;Oka et al 2014). Notably, PRP8, which can bind ubiquitin through its conserved JAMM (JAB1/MPN/Mov34 metalloenzyme) domain, was detected as an ubiquitin conjugate in affinity-purified particles in budding yeast, suggesting a means to reversibly modulate the activity of this protein (Bellare et al 2008).…”

Section: Discussionmentioning

confidence: 99%

An Rtf2 Domain-Containing Protein Influences Pre-mRNA Splicing and Is Essential for Embryonic Development in Arabidopsis thaliana

et al. 2015

View full text Add to dashboard Cite

Alternative splicing is prevalent in plants, but little is known about its regulation in the context of developmental and signaling pathways. We describe here a new factor that influences pre-messengerRNA (mRNA) splicing and is essential for embryonic development in Arabidopsis thaliana. This factor was retrieved in a genetic screen that identified mutants impaired in expression of an alternatively spliced GFP reporter gene. In addition to the known spliceosomal component PRP8, the screen recovered Arabidopsis RTF2 (AtRTF2), a previously uncharacterized, evolutionarily conserved protein containing a replication termination factor 2 (Rtf2) domain. A homozygous null mutation in AtRTF2 is embryo lethal, indicating that AtRTF2 is an essential protein. Quantitative RT-PCR demonstrated that impaired expression of GFP in atrtf2 and prp8 mutants is due to inefficient splicing of the GFP pre-mRNA. A genome-wide analysis using RNA sequencing indicated that 13-16% of total introns are retained to a significant degree in atrtf2 mutants. Considering these results and previous suggestions that Rtf2 represents an ubiquitin-related domain, we discuss the possible role of AtRTF2 in ubiquitin-based regulation of pre-mRNA splicing.KEYWORDS alternative splicing; C2HC2 zinc finger; intron retention; Rtf2 domain; ubiquitin ligase I T is increasingly recognized that cotranscriptional and posttranscriptional gene regulation is comparable to transcriptional regulation in intricacy and importance. Pre-mRNA splicing is a cotranscriptional process and a major determinant of transcript abundance and complexity (Reddy et al. 2013). Constitutive splicing refers to the use of only one set of splice sites to generate a single mature mRNA. By contrast, alternative splicing occurs when variable splice sites are selected, leading to the generation of more than one processed RNA product from a single pre-messenger RNA (mRNA). An individual gene can thus potentially encode multiple proteins, leading to a substantial increase in proteomic diversity (Chen and Manley 2009;Syed et al. 2012;Reddy et al. 2013).Recent work has established that alternative splicing is common in plants, affecting 60% of intron-containing genes . Alternative splicing has important roles in plant growth, development, abiotic stress tolerance, circadian rhythms, and pathogen defense (Staiger and Brown 2013). The most common outcome of alternative splicing in plants is intron retention Lan et al. 2013), which occurs when an intron fails to be spliced out of the premRNA. Retained introns frequently contain premature termination codons (PTCs) that can channel the transcript into the nonsense-mediated decay (NMD) pathway. Intron retention provides a means for "transcriptome tuning" (Braunschweig et al. 2014) and contributes to the post-transcriptional regulation of gene expression by reducing levels of inappropriately expressed transcripts Ge and Porse 2013).Alternative splicing is subject to elaborate regulation that relies on general and specific trans-acting factors as ...

show abstract

“…In this new study, knockdown of 26 out of these 33 splicing factors tested result in defective SCC (Sundaramoorthy et al, 2014). Downregulation of UBL5, an ubiquitin-like modifier involved in premRNA splicing, also results in similar defects in SCC in a separate study (Oka et al, 2014). These factors belong to different subcomplexes and are involved in a variety of steps, from early spliceosome assembly (e.g.…”

mentioning

confidence: 79%

Splicing together sister chromatids

Valcárcel

Malumbres

2014

The EMBO Journal

View full text Add to dashboard Cite

Splicing of pre‐mRNAs is a necessary step for expression of the majority of genes in higher eukaryotes, and its regulation through alternative splice site selection shapes their proteomes. Defects in multiple splicing factors result in aberrant mitotic progression, although the molecular basis for this observation has remained elusive. Recent papers in The EMBO Journal and EMBO Reports reveal that expression of sororin, a critical regulator that stabilizes cohesin rings in sister chromatids, is exquisitely sensitive to defects in the splicing machinery, thus explaining the striking link between spliceosome function and chromosome segregation.

show abstract

UBL5 is essential for pre‐mRNA splicing and sister chromatid cohesion in human cells

Cited by 44 publications

References 26 publications

Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion

Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion

An Rtf2 Domain-Containing Protein Influences Pre-mRNA Splicing and Is Essential for Embryonic Development in Arabidopsis thaliana

Splicing together sister chromatids

Contact Info

Product

Resources

About