RNA decay articles within Nature

mRNA that contains a premature termination codon (PTC) triggers a genetic compensation response that involves both transcription of its homologous genes and degradation of the mutated transcript by the nonsense-mediated decay pathway.

TUT4 and TUT7 mediate 3′ uridylation of mRNA transcripts, preferentially those with short poly(A) tails; in the absence of TUT4 and TUT7, oocytes cannot mature and female mice are infertile.

The authors assess the role of N⁶-methyladenosine in T cell development and function, and show that RNA methylation controls T cell homeostasis by regulating IL-7-mediated STAT5 activation.

The vertebrate-conserved and germline-specific RNA-binding protein DND1 recruits the CCR4–NOT deadenylase complex to destabilize its mRNA targets and is required for the maintenance of germline stem cells.

The application of genome-wide CRISPR–Cas9 screening coupled with a fluorescent reporter to interrogate the microRNA pathway reveals that continual transient phosphorylation of Argonaute 2 is required to maintain the global efficiency of microRNA-mediated repression.

Fat mass and obesity-associated protein (FTO) preferentially demethylates m⁶A_m, a modified adenosine that, when present at the 5′ end of certain mRNAs, positively influences mRNA stability by preventing DCP2-mediated decapping.

A method, termed hiCLIP, has been developed to determine the RNA duplexes bound by RNA-binding proteins, revealing an unforeseen prevalence of long-range duplexes in 3′ untranslated regions (UTRs), and a decreased incidence of SNPs in duplex-forming regions; the results also show that RNA structure is able to regulate gene expression.

A newly developed method, NAD captureSeq, has been used to show that bacteria cap the 5′-ends of some RNAs to protect against degradation, much as happens with eukaryotic messenger RNAs, although with a different modification: nicotinamide adenine dinucleotide.

The structure of mouse Dis3l2 bound to an oligoU substrate shows a funnel-like substrate-binding site with the RNA being fed into the active site along a path that is distinct from that seen in the related catalytic subunit of the exosome — 12 uracils of the oligoU-tailed RNA are recognized in a complex network of interactions, suggesting the basis for target specificity.

The mRNAs of higher eukaryotes are extensively modified internally with N⁶-methyladenosine, but the specific functional role of this modification has been unclear; here this modification on mRNA is shown to be recognized by several proteins, the modification and its recognition serve to regulate the RNA’s lifetime.

This study reports a global analysis of binding sites for over 200 RNA-binding proteins (RBPs) from 24 species; conserved RNA-binding motifs are identified, and their analysis allows prediction of interaction sites based on the sequence of the RNA-binding domain alone.

This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.

Staufen 1 (STAU1) protein binds regions of dsRNA in the 3′ UTR of mRNAs and promotes their degradation, a process known as SMD (Staufen-mediated mRNA decay). Although a specific stem-loop binding site had been defined for one SMD target, it was unclear how STAU1 was directed to other SMD targets that lack this structure. This paper reports that pairing of Alu element sequences in long non-coding RNAs (lncRNAs) and in the 3′ UTR of the SMD target generates a dsRNA structure that STAU1 recognizes. This result highlights a new function for lncRNAs.