Regulation of Poly(A) Tail and Translation during the Somatic Cell Cycle

Abstract

Poly(A) tails are critical for mRNA stability and translation. However, recent studies have challenged this view, showing that poly(A) tail length and translation efficiency are decoupled in non-embryonic cells. Using TAIL-seq and ribosome profiling, we investigate poly(A) tail dynamics and translational control in the somatic cell cycle. We find dramatic changes in poly(A) tail lengths of cell-cycle regulatory genes like CDK1, TOP2A, and FBXO5, explaining their translational repression in M phase. We also find that poly(A) tail length is coupled to translation when the poly(A) tail is <20 nucleotides. However, as most genes have >20 nucleotide poly(A) tails, their translation is regulated mainly via poly(A) tail length-independent mechanisms during the cell cycle. Specifically, we find that terminal oligopyrimidine (TOP) tract-containing transcripts escape global translational suppression in M phase and are actively translated. Our quantitative and comprehensive data provide a revised view of translational control in the somatic cell cycle.

Adenylation by testis-specific cytoplasmic poly(A) polymerase, PAPOLB/TPAP, is essential for spermatogenesis

“…1) [23]. This is consistent with the recent findings that the median length of poly(A) tails is 50–100 nt in mammalian cells, which is shorter than previously thought (150–250 nt), and that additional poly(A) tail elongation does not further contribute to translational enhancement except on maternal mRNAs [33,34,35]. Thus, if cytoplasmic polyadenylation by PAPOLB governs spermiogenesis, it is expected that the “true” target(s) possesses maternal mRNA-like short poly(A) tail(s).…”

Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

“…Using in vitro translation and m 7 GTP cap-affinity pulldown assays, we do not find general cap-dependent translation regulation by 4E-BP1 S83 phosphorylation. Although we did not find S83 phosphorylation affecting general cap-binding or capdependent translation, we cannot exclude the possibility that an mRNA subpopulation is regulated by S83-phosphorylated 4E-BP1, such as terminal oligopyrimidine tract (TOP)-containing mRNAs that are reported to be translationally active during mitosis (43). A recent study shows that the interaction between the C-terminal loop with eIF4E is required for eIF4F complex formation and translation repression in vivo using 4E-BP1 truncation mutants, which, in light of our results, prompts the examination of other loop residues (36).…”

An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression

“…7). The fact that Mtr4/ZFC3H1 substrates have long poly(A) tails, which is in contrast to NEXT targets that largely lack poly(A) tails (Meola et al 2016), may help explain their efficient ribosome association (Peng et al 2008;Park et al 2016). It is noteworthy that although eRNAs are largely nonpolyadenylated (Djebali et al 2012;Andersson et al 2014a), we recently identified a class of poly(A) + eRNAs that are stabilized by Mtr4/ZFC3H1 knockdown.…”