News
Cell Reports, 2021, 36, 109633
Using the dynamic observation technique, Ribo-Seq, we have deciphered the genetic mechanisms governing the speed of translation of messenger RNA. We show that codon-specific translation elongation dynamics are modulated by Not4 and Not5, in coordination with Rli1 and opposing eIF5A function, and according to codon optimality to produce a soluble proteome. We propose that this regulation occurs by dynamic condensates that limit mRNA solubility and exclude eIF5A.
Allen G.E., Panasenko O.O., Villanyi Z., Zagatti M., Weiss B., Pagliazzo L., Huch S., Polte C., Zahoran Z., Hughes C.S., Pelechano V., Ignatova Z., Collart M.A.
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Abstract
In this work, we show that Not4 and Not5 from the Ccr4-Not complex modulate translation elongation dynamics and change ribosome A-site dwelling occupancy in a codon-dependent fashion. These codon-specific changes in not5Δ cells are very robust and independent of codon position within the mRNA, the overall mRNA codon composition, or changes of mRNA expression levels. They inversely correlate with codon-specific changes in cells depleted for eIF5A and positively correlate with those in cells depleted for ribosome-recycling factor Rli1. Not5 resides in punctate loci, co-purifies with ribosomes and Rli1, but not with eIF5A, and limits mRNA solubility. Overexpression of wild-type or non-complementing Rli1 and loss of Rps7A ubiquitination enable Not4 E3 ligase-dependent translation of polyarginine stretches. We propose that Not4 and Not5 modulate translation elongation dynamics to produce a soluble proteome by Rps7A ubiquitination, dynamic condensates that limit mRNA solubility and exclude eIF5A, and a moonlighting function of Rli1.