TY - JOUR
T1 - Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome
AU - Agranat-Tamir, Lily
AU - Shomron, Noam
AU - Sperling, Joseph
AU - Sperling, Ruth
N1 - Funding Information:
The US NIH [RO1 GM079549 to R. S. and J.S.]; the Helen and Milton Kimmelman Center for Biomolecular Structure and Assembly at the Weizmann Institute of Science (to J.S.) for financial support. Funding for open access charge: Waived by Oxford University Press.
PY - 2014/4
Y1 - 2014/4
N2 - MicroRNAs (miRNAs) are central regulators of gene expression, and a large fraction of them are encoded in introns of RNA polymerase II transcripts. Thus, the biogenesis of intronic miRNAs by the microprocessor and the splicing of their host introns by the spliceosome require coordination between these processing events. This cross-talk is addressed here. We show that key microprocessor proteins Drosha and DGCR8 as well as pre-miRNAs cosediment with supraspliceosomes, where nuclear posttranscriptional processing is executed. We further show that inhibition of splicing increases miRNAs expression, whereas knock-down of Drosha increases splicing. We identified a novel splicing event in intron 13 of MCM7, where the miR-106b-25 cluster is located the unique splice isoform includes a hosted pre-miRNA in the extended exon and excludes its processing. This indicates a possible mechanism of altering the levels of different miRNAs originating from the same transcript. Altogether, our study indicates interplay between the splicing and microprocessor machineries within a supraspliceosome context.
AB - MicroRNAs (miRNAs) are central regulators of gene expression, and a large fraction of them are encoded in introns of RNA polymerase II transcripts. Thus, the biogenesis of intronic miRNAs by the microprocessor and the splicing of their host introns by the spliceosome require coordination between these processing events. This cross-talk is addressed here. We show that key microprocessor proteins Drosha and DGCR8 as well as pre-miRNAs cosediment with supraspliceosomes, where nuclear posttranscriptional processing is executed. We further show that inhibition of splicing increases miRNAs expression, whereas knock-down of Drosha increases splicing. We identified a novel splicing event in intron 13 of MCM7, where the miR-106b-25 cluster is located the unique splice isoform includes a hosted pre-miRNA in the extended exon and excludes its processing. This indicates a possible mechanism of altering the levels of different miRNAs originating from the same transcript. Altogether, our study indicates interplay between the splicing and microprocessor machineries within a supraspliceosome context.
UR - http://www.scopus.com/inward/record.url?scp=84899008312&partnerID=8YFLogxK
U2 - 10.1093/nar/gkt1413
DO - 10.1093/nar/gkt1413
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AN - SCOPUS:84899008312
SN - 0305-1048
VL - 42
SP - 4640
EP - 4651
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 7
ER -