title: DROSHA targets its own transcript to modulate alternative splicing.
abstract: The nuclear RNase III enzyme DROSHA interacts with its cofactor DGCR8 to form the Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving hairpin structures embedded in primary transcripts. Apart from its central role in the biogenesis of miRNAs, DROSHA is also known to recognize and cleave miRNA-like hairpins in a subset of transcripts without apparent small RNA production. Here, we report that the humanDROSHAtranscript is one such noncanonical target of DROSHA. MammalianDROSHAgenes have evolved a conserved hairpin structure spanning a specific exon-intron junction, which serves as a substrate for the Microprocessor in human cells but not in murine cells. We show that it is this hairpin element that decides whether the overlapping exon is alternatively or constitutively spliced. We further demonstrate that DROSHA promotes skipping of the overlapping exon in human cells independently of its cleavage function. Our findings add to the expanding list of noncanonical DROSHA functions.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Dooyoung
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Science, Hanyang University, Seoul 04763, Republic of Korea.
authors.forename: Jin-Wu
authors.initials: JW
authors.lastname: Nam
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.|Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.|Plant Genomics and Breeding Institute, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Chanseok
authors.initials: C
authors.lastname: Shin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005091:Exons; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences; D051379:Mice; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; C513400:Drosha protein, mouse; D043244:Ribonuclease III
keywords: DROSHA; Microprocessor; alternative splicing