Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex

The S. pombe orthologue of the human PAXT connection, Mtl1-Red1 Core (MTREC), is an eleven-subunit complex that targets cryptic unstable transcripts (CUTs) to the nuclear RNA exosome for degradation. It encompasses the canonical poly(A) polymerase Pla1, responsible for polyadenylation of nascent RNA transcripts as part of the cleavage and polyadenylation factor (CPF/CPSF). In this study we identify and characterise the interaction between Pla1 and the MTREC complex core component Red1 and analyse the functional relevance of this interaction in vivo. Our crystal structure of the Pla1-Red1 complex shows that a 58-residue fragment in Red1 binds to the RNA recognition motif domain of Pla1 and tethers it to the MTREC complex. Structure-based Pla1-Red1 interaction mutations show that Pla1, as part of MTREC complex, hyper-adenylates CUTs for their efficient degradation. Interestingly, the Red1-Pla1 interaction is also required for the efficient assembly of the fission yeast facultative heterochromatic islands. Together, our data suggest a complex interplay between the RNA surveillance and 3'-end processing machineries. Here the authors show how the MTREC core protein Red1 binds to and sequesters Pla1 from the 3'-end processing machinery to hyperadenylate cryptic unstable transcripts and target them to the exosome for efficient degradation.

Automated summary

In this study, the interaction between the MTREC core protein Red1 and Pla1 is characterized and its functional relevance in vivo is assessed. The authors found that the Red1-Pla1 interaction leads to hyperadenylation of CUTs, facilitating their degradation. Additionally, this interaction is required for the efficient assembly of facultative heterochromatic islands in fission yeast.