title: U1 snRNP-mediated poly(A) site suppression: beneficial and deleterious for mRNA fate.
abstract: The spliceosomal component U1snRNP commits pre-mRNAs to the splicing pathway. Recently, a nuclear RNA surveillance function has been ascribed to U1, namely the suppression of intronic polyadenylation sites. This surveillance holds regulatory potential as it alters the 3' ends of certain receptor tyrosine kinase mRNAs. However, suppression of 3' end processing by U1 snRNP is also the cause of a severe genetic disorder. We described a 3'UTR point mutation creating a 5'SS leading to U1-mediated suppression of 3' end formation. Thus, the inhibitory function of U1 is both beneficial and deleterious where misled. The exact mechanism of how U1 interferes with 3' end processing remains unclear. According to our data, U1 snRNP already interferes with cleavage or poly(A) site selection instead of directly inhibiting poly(A) polymerase as previously assumed. Here, we present alternative models for U1-mediated poly(A) site suppression and discuss the implications for RNA quality control and disease-related mutations.
authors: Institute for Virology, Hannover Medical School, Hannover, Germany.
authors: Jörg
authors: J
authors: Langemeier
authors: Maximilian
authors: M
authors: Radtke
authors: Jens
authors: J
authors: Bohne
mesh_terms: D020413:3' Untranslated Regions; D006678:HIV / Q000235:genetics / Q000378:metabolism; D007438:Introns; D017354:Point Mutation; D011061:Poly A / Q000235:genetics / Q000378:metabolism*; D026723:Polyadenylation; D059367:RNA Cleavage; D022821:RNA Splice Sites; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D022821:RNA Splice Sites; D012333:RNA, Messenger; D012367:RNA, Viral; D017412:Ribonucleoprotein, U1 Small Nuclear; D011061:Poly A
keywords: 3′ UTR; RNA processing; U1 site; genetic disease; polyadenylation