Yeast poly(A)-binding protein (Pab1) controls translation initiation in vivo primarily by blocking mRNA decapping and decay.

Poly(A)-binding protein (Pab1 in yeast) is involved in mRNA decay and translation initiation, but its molecular functions are incompletely understood. We found that auxin-induced degradation of Pab1 reduced bulk mRNA and polysome abundance in WT but not in a mutant lacking the catalytic subunit of decapping enzyme (Dcp2), suggesting that enhanced decapping/degradation is a major driver of reduced translation at limiting Pab1. An increased median poly(A) tail length conferred by Pab1 depletion was likewise not observed in the dcp2Δ mutant, suggesting that mRNA isoforms with shorter tails are preferentially decapped/degraded at limiting Pab1. In contrast to findings on mammalian cells, the translational efficiencies (TEs) of many mRNAs were altered by Pab1 depletion; however, these changes were diminished in dcp2Δ cells, suggesting that reduced mRNA abundance is also a major driver of translational reprogramming at limiting Pab1. Thus, assembly of the closed-loop mRNP via PABP-eIF4G interaction appears to be dispensable for wild-type translation of most transcripts at normal mRNA levels. Interestingly, histone mRNAs and proteins were preferentially diminished on Pab1 depletion in DCP2 but not dcp2Δ cells, accompanied by activation of internal cryptic promoters in the manner expected for reduced nucleosome occupancies, implicating Pab1 in post-transcriptional control of histone gene expression.