The Role of Terminal Uridyl Transferases in the Circadian Rhythm

Abstract

The 3′ terminal oligo-uridylation, a post-transcriptional mRNA modification, is conserved among eukaryotes and drives mRNA degradation, thereby affecting several key biological processes such as animal development and viral infection. Our TAIL-seq experiment of mouse liver mRNA collected from six zeitgeber times reveals transcripts with rhythmic poly(A) tail lengths and demonstrates that overall 3′ terminal uridylation frequencies at mRNA poly(A) tail very-ends undergo rhythmic change. Consistently, major terminal uridylyl transferases, TUT4 and TUT7, have cycling protein expression in mouse liver corresponding to 3′ terminal uridylation rhythms, indicating that the cycling expression of TUTases correlates with the rhythmic pattern of uridylation. Furthermore, the double knockdown of TUT4 and TUT7 in U2OS cells lengthens the circadian period and decreases the rhythmic amplitude of clock gene expression. Our work thoroughly profiles the dynamic changes in poly(A) tail lengths and terminal modifications and uncovers uridylation as a post-transcriptional modulator in the mammalian circadian clock.

Revealing the hidden RBP–RNA interactions with RNA modification enzyme‐based strategies

“…In summary, mono-and oligo-uridylation participate in biogenesis, decay, and function of coding and noncoding RNA. In many cases, oligo-U tags often trigger spatiotemporally-controlled RNA degradation, as well as abnormal RNA and viral RNA clearance, which plays key roles in embryonic development, cell cycle, circadian rhythm, immunity, and diseases (Beta & Balatsos, 2018;Chang et al, 2018;Le Pen et al, 2018;Liu et al, 2020;Reyes & Ross, 2016;Song et al, 2023).…”