Abstract
The large C2H2-Zinc Finger (C2H2-ZNF) gene family has rapidly expanded in primates through gene duplication. There is consequently considerable sequence homology between family members at both the nucleotide and amino acid level, allowing for coordinated regulation and shared functions. Here we show that multiple C2H2-ZNF mRNAs experience differential polyadenylation resulting in populations with short and long poly(A) tails. Furthermore, a significant proportion of C2H2-ZNF mRNAs are retained in the nucleus. Intriguingly, both short poly(A) tails and nuclear retention can be specified by the repeated elements that encode zinc finger motifs. These Zinc finger Coding Regions (ZCRs) appear to restrict polyadenylation of nascent RNAs and at the same time impede their export. However, the polyadenylation process is not necessary for nuclear retention of ZNF mRNAs. We propose that inefficient polyadenylation and export may allow C2H2-ZNF mRNAs to moonlight as non-coding RNAs or to be stored for later use.
Highlights
Zinc-finger (ZNF)-containing proteins are among the largest families of proteins in the human genome
We evaluated six C2H2-ZNF mRNAs with different properties, some of which were previously identified as bimorphic[17] and most of which share similar metabolism profiles (“biotypes”) as classified by Mukherjee et al.[19] who evaluated various properties of mRNAs including nuclear/cytoplasmic distribution, synthesis, processing, translation and decay rates (Table 1)
We evaluated the poly(A) tail of the ZNF12 reporter via RNAseH northern blotting and found that, like the endogenous ZNF12 transcript (Fig. 1B), the vast majority of mRNA produced lacks poly(A) (Fig. 3D, Supplementary Fig. S6).Taken together these results suggest that sequence elements present in the 3′UTR and/or ORF of ZNF12 can confer nuclear retention, and restrict the length of the poly(A) tail
Summary
Zinc-finger (ZNF)-containing proteins are among the largest families of proteins in the human genome. The linker domains between individual ZNFs are targeted by the TOPK/PBK kinase during mitosis to induce dissociation of these proteins from condensing chromatin[13,14] These highly conserved repeated protein motifs may serve functions other than binding DNA. Four miRNAs can target the repeated regions encoding zinc fingers found in related C2H2-ZNF mRNAs15,16. A large group of C2H2-ZNF transcripts are decayed more slowly in stem cells than in fully differentiated fibroblasts[18] This could be facilitated by recognition of shared sequence elements by a stem cell or fibroblast-specific RBP or miRNA. We show that repetitive sequence elements encoding C2H2-ZNF motifs (Zinc finger Coding Regions or ZCRs) act as poly(A) limiting elements, resulting in a sub-population of mRNAs that have short poly(A) tails. We provide evidence that C2H2-ZNF mRNAs are retained in the nucleus through mechanisms that do not require polyadenylation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
