A novel CUCU modification of poly(A) tail signals the end of mRNA

Igor Morozov[1] Meriel G. Jones[1] Dave G. Spiller[1] Joseph Strauss[2] Mark X Caddick[

Author address: 

School of Biological Sciences, The University of Liverpool, Crown Street, Liverpool L69 7ZB, UK 2Fungal Genetics and Genomics Unit, Austrian Institute of Technology and BOKU University Vienna, Muthgasse 18 A-1190 Vienna, Austria

Abstract: 

In eukaryotes differential transcript degradation represents an integral component of gene regulation. Generally the limiting step in mRNA turnover is deadenylation, which triggers translational repression and 5’ decapping once the length of poly(A) tail reached about 15 A residues. We have recently shown that in Aspergillus nidulans both the Caf1 and Ccr4 orthologues are functionally distinct deadenylases: Ccr4 is responsible for basal degradation while Caf1 is required for the regulated degradation of specific transcripts and the variation in Processing (P) body formation, which occurs in response to a wide range of stimuli. Disruption of the Ccr4-Caf1-Not complex leads to premature, poly(A) independent decapping. We have shown that decapping is correlated with a novel transcript modification, the addition of a CUCU sequence. This 3’ modification of mRNA occurs precisely at the point decapping is triggered. The addition of the CUCU based sequence tag requires a nucleotidyltransferase CutA, the disruption of which significantly stabilises mRNA and blocks the formation of P-bodies. Intriguingly, the key enzyme complex responsible for deadenylation and therefore degradation, Ccr4-Caf1-Not, also protects mRNA from premature modification and deadenylation independent decapping. We propose that 3’ modification of adenylated mRNA, which is likely to represent a common eukaryotic process, primes the transcript for dissociation from ribosomes, decapping and efficient degradation (1). References: 1. Morozov IY, Jones MG, Razak AA, Rigden DJ and Caddick MX. CUCU modification of mRNA promotes decapping and transcript degradation in Aspergillus nidulans. Mol Cell Biol, 2010, V.30 (4) in press.
2010

abstract No: 

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Full conference title: 

10th EUROPEAN CONFERENCE ON FUNGAL GENETICS
    • ECFG 10th (2010)