Pre-mRNA structures forming circular RNAs

Publication date: Available online 14 August 2019Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Justin R. Welden, Stefan StammAbstractCircular RNAs are a recently discovered class of RNAs formed by covalently linking the 5′ and 3′ end of an RNA. Pre-mRNAs generate circular RNAs through a back-splicing mechanism. Whereas in linear splicing a 5′ splice site is connected to a downstream 3′ splice site, in back-splicing the 5′ splice site is connected to an upstream 3′ splice site. Both mechanisms use the spliceosome for catalysis. For back-splicing to occur, the back-splice sites must frequently be brought into close proximity, which is achieved through the formation of secondary structures in the pre-mRNA. In general, these pre-mRNA structures are formed by RNA base pairing between complementary sequences flanking the back-splicing sites. Proteins can abolish these RNA structures through binding to one of the complementary strands. However, proteins can also promote back-splicing without strong RNA structures through multimerization after binding to intronic regions flanking circular exons. In humans, Alu-elements comprising around 11% of the human genome are the best-characterized RNA-elements generating structures promoting circular RNA formation. Thus, intronic pre-mRNA structures contribute to the formation of circular RNAs.

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - August 14, 2019 Category: Genetics & Stem Cells Source Type: research