A DIStinctively novel exoribonuclease that really likes U

Abstract

Regulated degradation plays a major role in determining the levels of both non-coding (miRNA) and coding (mRNA) transcripts. Thus, insights into the factors and pathways that influence this process have broad, interdisciplinary implications. New findings by Malecki et al (2013), Lubas et al (2013), and Chang et al (2013) identify the protein Dis3L2 as a major player in the 3′–5′ exonucleolytic decay of transcripts. Furthermore, they demonstrate a strong connection between terminal uridylation of the RNA substrate and enzymatic activity.

Figure 1

Dis3L2 is a new player in a major pathway of RNA decay. Many mRNAs normally undergo poly(A) tail removal by deadenylases as a first step prior to their decay by an exonucleolytic mechanism. Recruitment of the Lsm1-7 complex to the 3′ end of a mRNA triggers decapping by the Dcp1–Dcp2 complex, making the RNA accessible to the 5′–3′ exoribonuclease Xrn1. Degradation can also occur in the 3′→5′ direction if the exosome complex is recruited to the 3′ end of deadenylated transcript. In this pathway, short-capped RNA oligomers generated by the exosome are acted on by the scavenger-decapping enzyme DcpS. The recent observations of Malecki et al (2013) and Lubas et al (2013) indicate that the 3′–5′ decay of mRNAs can also occur in an exosome-independent and uridylation-dependent manner. A TUTase enzyme adds a short poly(U) tract to a deadenylated mRNA that becomes an ideal landing pad for the 3′–5′ exoribonuclease Dis3L2. Chang et al (2013) demonstrated that a similar uridylation/Dis3L2-mediated 3′–5′ decay pathway also acts on let7 pre-miRNAs.