Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome.
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.
Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel, Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel and Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Lily
L
Agranat-Tamir
Noam
N
Shomron
Joseph
J
Sperling
Ruth
R
Sperling
D017398:Alternative Splicing; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D035683:MicroRNAs / Q000378:metabolism*; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology; D059368:RNA Isoforms / Q000032:analysis; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D043244:Ribonuclease III / Q000037:antagonists & inhibitors; D013141:Spiro Compounds / Q000494:pharmacology; D017381:Spliceosomes / Q000378:metabolism*
D035683:MicroRNAs; D011714:Pyrans; D059368:RNA Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; D013141:Spiro Compounds; C553684:spliceostatin A; C517918:DROSHA protein, human; D043244:Ribonuclease III; D064168:Minichromosome Maintenance Complex Component 7