Microprocessor-dependent processing of splice site overlapping microRNA exons does not result in changes in alternative splicing

Pianigiani, Giulia; Licastro, Danilo; Fortugno, Paola; Castiglia, Daniele; Petrović, Ivana; Pagani, Franco

doi:10.1261/rna.063438.117

Cited by 13 publications

(18 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found some pre-miRNAs overlapping intron-exon junctions. These SO-miRNAs may be involved in regulating gene expression in cynomolgus macaques, whereby microprocessor complex-dependent cleavage of SO-miRNA exons could result in premature transcriptional termination of coding genes, as described in humans (Pianigiani et al, 2018). Two pairs of distinct antisense miRNAs were found in this study.…”

Section: Discussionsupporting

confidence: 64%

Analysis of conserved miRNAs in cynomolgus macaque genome using small RNA sequencing and homology searching

Huang

Liu³

et al. 2020

PeerJ

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are important regulators that fine-tune diverse cellular activities. Cynomolgus macaques (Macaca fascicularis) are used extensively in biomedical and pharmaceutical research; however, substantially fewer miRNAs have been identified in this species than in humans. Consequently, we investigated conserved miRNA profiles in cynomolgus macaques by homology searching and small RNA sequencing. In total, 1,455 high-confidence miRNA gene loci were identified, 408 of which were also confirmed by RNA sequencing, including 73 new miRNA loci reported in cynomolgus macaques for the first time. Comparing miRNA expression with age, we found a positive correlation between sequence conservation and expression levels during miRNA evolution. Additionally, we found that the miRNA gene locations in cynomolgus macaque genome were very flexible. Most were embedded in intergenic spaces or introns and clustered together. Several miRNAs were found in certain gene locations, including 64 exon-resident miRNAs, six splice-site-overlapping miRNAs (SO-miRNAs), and two pairs of distinct mirror miRNAs. We also identified 78 miRNA clusters, 68 of which were conserved in the human genome, including 10 large miRNA clusters predicted to regulate diverse developmental and cellular processes in cynomolgus macaque. Thus, this study not only expands the number of identified miRNAs in cynomolgus macaques but also provides clues for future research on the differences in miRNA repertoire between macaques and humans.

show abstract

Section: Discussionsupporting

confidence: 64%

Analysis of conserved miRNAs in cynomolgus macaque genome using small RNA sequencing and homology searching

Huang

Liu³

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…Despite this general SF3B1 decreased expression, we carried out RT-PCR experiments to study splicing events specifically altered upon downregulation of SF3B1, in order to evaluate the capacity of SF3B1 wt INS and SF3B1 K700E INS to compensate for the splicing defects caused by SF3B1 depletion. We decided to study specific exon skipping events in RBM5, DUSP11, CCNA2, and STK6, the splicing of which was known to be modified upon either SF3B1 silencing [22,30] or treatment by the spliceosome inhibitor spliceotastin A [31]. Depletion of SF3B1 in siRNA-only transfected cells or in K562 cells co-transfected with the empty vector favored skipping of exon 6 in RBM5, of exon 6 in DUSP11, of exon 5 in CCNA2 and of exons 4-5-6 in STK6 ( Figure 2D,E), as previously described.…”

Section: Insmentioning

confidence: 99%

Human Cancer-Associated Mutations of SF3B1 Lead to a Splicing Modification of Its Own RNA

Bergot

Lippert

Douet‐Guilbert

et al. 2020

Cancers

View full text Add to dashboard Cite

Deregulation of pre-mRNA splicing is observed in many cancers and hematological malignancies. Genes encoding splicing factors are frequently mutated in myelodysplastic syndromes, in which SF3B1 mutations are the most frequent. SF3B1 is an essential component of the U2 small nuclear ribonucleoprotein particle that interacts with branch point sequences close to the 3’ splice site during pre-mRNA splicing. SF3B1 mutations mostly lead to substitutions at restricted sites in the highly conserved HEAT domain, causing a modification of its function. We found that SF3B1 was aberrantly spliced in various neoplasms carrying an SF3B1 mutation, by exploring publicly available RNA sequencing raw data. We aimed to characterize this novel SF3B1 transcript, which is expected to encode a protein with an insertion of eight amino acids in the H3 repeat of the HEAT domain. We investigated the splicing proficiency of this SF3B1 protein isoform, in association with the most frequent mutation (K700E), through functional complementation assays in two myeloid cell lines stably expressing distinct SF3B1 variants. The yeast Schizosaccharomyces pombe was also used as an alternative model. Insertion of these eight amino acids in wild-type or mutant SF3B1 (K700E) abolished SF3B1 essential function, highlighting the crucial role of the H3 repeat in the splicing function of SF3B1.

show abstract

“…We conclude that the exonic flanking regions contain more reliable information related to the processing of payload than the flanking sequences in the primary sequence. For miRNAs this can be explained in particular by sequence motifs associated with microprocessor activity [31,32]. For snoRNAs, their obligatory location in (usually short) introns also supports a connection with splicing, see also [7,33].…”

Section: Exonic Sequences Onlymentioning

confidence: 91%

Supervised and Unsupervised Classification of lncRNA Subtypes

Sen¹,

Fallmann²,

Walter

et al. 2020

Preprint

View full text Add to dashboard Cite

Many small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding (lncRNA) host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless there is mounting evidence that the host genes have biological functions. No obvious connections between the function of the host genes and the function of their payloads have been reported. Here we inverstigate whether there is an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNAs host genes can be distinguished based on sequence and structure features. A positive answer would imply a correlation between host genes and their payload. While the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads, this is no longer the case when only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. We conclude therefore, that MIRHGs and SNHGs do not form separate non-coding RNA classes that are distinct from each other or from lncRNAs without payloads.

show abstract

Microprocessor-dependent processing of splice site overlapping microRNA exons does not result in changes in alternative splicing

Cited by 13 publications

References 47 publications

Analysis of conserved miRNAs in cynomolgus macaque genome using small RNA sequencing and homology searching

Analysis of conserved miRNAs in cynomolgus macaque genome using small RNA sequencing and homology searching

Human Cancer-Associated Mutations of SF3B1 Lead to a Splicing Modification of Its Own RNA

Supervised and Unsupervised Classification of lncRNA Subtypes

Contact Info

Product

Resources

About