Repeated sequences encoding Cys2His2 zinc finger motifs influence mRNA polyadenylation and localization
Date
2017
Authors
Jalkanen, Aimee L., author
Wilusz, Carol, advisor
Wilusz, Jeffrey, advisor
Bailey, Susan, committee member
Bouma, Gerrit, committee member
Thamm, Douglas, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
The Cysteine2 Histidine2 zinc finger (C2H2-ZNF) proteins are a vast family with over 700 members in primates, many of which are transcription factors with important roles in development, differentiation, cell cycle progression, and tumor suppression. Due to the sheer number of C2H2-ZNF proteins and their roles in modulating expression of other genes, any mechanism for coordinating their expression could have wide-ranging impacts on cell function and phenotype. Previously, a large subset of C2H2-ZNF transcripts were determined to have significant populations with short poly(A) tails. Here, we show that multiple C2H2-ZNF mRNAs accumulate with very short or undetectable poly(A) tails, even when newly transcribed. Furthermore, these C2H2-ZNF mRNAs are restricted to the nucleus. Reporter mRNAs with sequences from the ZNF12 open reading frame (ORF) and/or the 3' untranslated region (3' UTR) have short poly(A) tails and are retained in the nucleus. Deletion analysis suggests that repeated sequence elements in the ZNF12 mRNA that code for zinc finger protein motifs are important in controlling both poly(A) tail length and nuclear localization. Remnants of C2H2-ZNF motif sequences found in the ZNF12 3' UTR are also able to confer short poly(A) tails and nuclear retention. Finally, we use RNA-fluorescence in situ hybridization (RNA-FISH) to reveal that ZNF12 reporter transcripts are found in foci within the nucleus that could represent sites for storage or processing. Overall, our findings suggest repeated sequence elements encoding C2H2-ZNF protein motifs play a dual role as regulatory elements that may coordinate expression of the C2H2-ZNF protein family by controlling post-transcriptional events.