Changes in poly(A) tail length dynamics from the loss of the circadian deadenylase Nocturnin

mRNA poly(A) tails are important for mRNA stability and translation, and enzymes that regulate the poly(A) tail length significantly impact protein profiles. There are eleven putative deadenylases in mammals, and it is thought that each targets specific transcripts, although this has not been clearly demonstrated. Nocturnin (NOC) is a unique deadenylase with robustly rhythmic expression and loss of Noc in mice (Noc KO) results in resistance to diet-induced obesity. In an attempt to identify target transcripts of NOC, we performed “poly(A)denylome” analysis, a method that measures poly(A) tail length of transcripts in a global manner, and identified 213 transcripts that have extended poly(A) tails in Noc KO liver. These transcripts share unexpected characteristics: they are short in length, have long half-lives, are actively translated, and gene ontology analyses revealed that they are enriched in functions in ribosome and oxidative phosphorylation pathways. However, most of these transcripts do not exhibit rhythmicity in poly(A) tail length or steady-state mRNA level, despite Noc’s robust rhythmicity. Therefore, even though the poly(A) tail length dynamics seen between genotypes may not result from direct NOC deadenylase activity, these data suggest that NOC exerts strong effects on physiology through direct and indirect control of target mRNAs.