mRNA degradation coupled with nascent peptide-mediated translation elongation arrest

Abstract

Cystathionine γ-synthase (CGS) catalyzes the key step in methionine biosynthesis. Stability of CGS1 mRNA is feedback-regulated in response to S-adenosyl-L-methionine (SAM). This regulation occurs during translation, and a short stretch of amino acid sequence termed the MTO1 region, encoded by CGS1 itself, acts in cis.
Studies using in vitro translation revealed that SAM causes temporal translation elongation arrest at Ser⁹⁴ located just downstream of the MTO1 region. Ribosome is stalled at the translocation step, and it's A-site is occupied by peptidyl-tRNA^Ser. Following this translation arrest, mRNA degradation event occurs near the 5'-edge of the stalled ribosome, and 3'-fragments of CGS1 mRNA are produced as degradation intermediate.
In mRNA quality control systems, such as NMD, mRNA degradation is induced after an empty A-site is recognized by responsive factors. The fact that the A-site is occupied by peptidyl-tRNA in CGS1 system suggests the degradation mechanisms are different.