RRC ID 70468
Author Bai W, Wells ML, Lai WS, Hicks SN, Burkholder AB, Perera L, Kimmel AR, Blackshear PJ.
Title A post-transcriptional regulon controlled by TtpA, the single tristetraprolin family member expressed in Dictyostelium discoideum.
Journal Nucleic Acids Res
Abstract Post-transcriptional processes mediated by mRNA binding proteins represent important control points in gene expression. In eukaryotes, mRNAs containing specific AU-rich motifs are regulated by binding of tristetraprolin (TTP) family tandem zinc finger proteins, which promote mRNA deadenylation and decay, partly through interaction of a conserved C-terminal CNOT1 binding (CNB) domain with CCR4-NOT protein complexes. The social ameba Dictyostelium discoideum shared a common ancestor with humans more than a billion years ago, and expresses only one TTP family protein, TtpA, in contrast to three members expressed in humans. Evaluation of ttpA null-mutants identified six transcripts that were consistently upregulated compared to WT during growth and early development. The 3'-untranslated regions (3'-UTRs) of all six 'TtpA-target' mRNAs contained multiple TTP binding motifs (UUAUUUAUU), and one 3'-UTR conferred TtpA post-transcriptional stability regulation to a heterologous mRNA that was abrogated by mutations in the core TTP-binding motifs. All six target transcripts were upregulated to similar extents in a C-terminal truncation mutant, in contrast to less severe effects of analogous mutants in mice. All six target transcripts encoded probable membrane proteins. In Dictyostelium, TtpA may control an 'RNA regulon', where a single RNA binding protein, TtpA, post-transcriptionally co-regulates expression of several functionally related proteins.
Volume 49(20)
Pages 11920-11937
Published 2021-11-18
DOI 10.1093/nar/gkab983
PII 6414599
PMID 34718768
PMC PMC8599788
MeSH 3' Untranslated Regions Dictyostelium / genetics* Dictyostelium / metabolism Mutation Protozoan Proteins / genetics Protozoan Proteins / metabolism* RNA Stability RNA, Messenger / chemistry RNA, Messenger / genetics RNA, Messenger / metabolism Regulon* Tristetraprolin / genetics Tristetraprolin / metabolism*
IF 11.502
Resource
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