title: Long noncoding RNAs: Re-writing dogmas of RNA processing and stability.
abstract: Most of the human genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs. Many of these transcripts have a 5' cap and a poly(A) tail, yet some of the most abundant long noncoding RNAs are processed in unexpected ways and lack these canonical structures. Here, I highlight the mechanisms by which several of these well-characterized noncoding RNAs are generated, stabilized, and function. The MALAT1 and MEN β (NEAT1_2) long noncoding RNAs each accumulate to high levels in the nucleus, where they play critical roles in cancer progression and the formation of nuclear paraspeckles, respectively. Nevertheless, MALAT1 and MEN β are not polyadenylated as the tRNA biogenesis machinery generates their mature 3' ends. In place of a poly(A) tail, these transcripts are stabilized by highly conserved triple helical structures. Sno-lncRNAs likewise lack poly(A) tails and instead have snoRNA structures at their 5' and 3' ends. Recent work has additionally identified a number of abundant circular RNAs generated by the pre-mRNA splicing machinery that are resistant to degradation by exonucleases. As these various transcripts use non-canonical strategies to ensure their stability, it is becoming increasingly clear that long noncoding RNAs may often be regulated by unique post-transcriptional control mechanisms. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: wilusz@mail.med.upenn.edu.
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Wilusz
mesh_terms: D002467:Cell Nucleus / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D011061:Poly A / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000235:genetics
chemical_list: D012322:RNA Precursors; D062085:RNA, Long Noncoding; D020537:RNA, Small Nucleolar; D011061:Poly A
keywords: CircRNA; Circular RNA; MALAT1; MEN β; NEAT1; Polyadenylation; Pre-mRNA splicing; RNA stability; Sno-lncRNA; Triple helix; tRNA-like