PMID- 34718768 OWN - NLM STAT- MEDLINE DCOM- 20211227 LR - 20211227 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 49 IP - 20 DP - 2021 Nov 18 TI - A post-transcriptional regulon controlled by TtpA, the single tristetraprolin family member expressed in Dictyostelium discoideum. PG - 11920-11937 LID - 10.1093/nar/gkab983 [doi] AB - 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. CI - Published by Oxford University Press on behalf of Nucleic Acids Research 2021. FAU - Bai, Wenli AU - Bai W AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. FAU - Wells, Melissa L AU - Wells ML AD - The Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. FAU - Lai, Wi S AU - Lai WS AD - The Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. FAU - Hicks, Stephanie N AU - Hicks SN AD - The Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. FAU - Burkholder, Adam B AU - Burkholder AB AD - Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. FAU - Perera, Lalith AU - Perera L AD - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. FAU - Kimmel, Alan R AU - Kimmel AR AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. FAU - Blackshear, Perry J AU - Blackshear PJ AUID- ORCID: 0000-0002-9561-8529 AD - The Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. AD - The Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. LA - eng PT - Journal Article PT - Research Support, N.I.H., Intramural PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (3' Untranslated Regions) RN - 0 (Protozoan Proteins) RN - 0 (RNA, Messenger) RN - 0 (Tristetraprolin) SB - IM MH - 3' Untranslated Regions MH - Dictyostelium/*genetics/metabolism MH - Mutation MH - Protozoan Proteins/genetics/*metabolism MH - RNA Stability MH - RNA, Messenger/chemistry/genetics/metabolism MH - *Regulon MH - Tristetraprolin/genetics/*metabolism PMC - PMC8599788 EDAT- 2021/11/01 06:00 MHDA- 2021/12/28 06:00 PMCR- 2021/10/30 CRDT- 2021/10/31 21:15 PHST- 2021/10/12 00:00 [accepted] PHST- 2021/10/05 00:00 [revised] PHST- 2021/05/06 00:00 [received] PHST- 2021/11/01 06:00 [pubmed] PHST- 2021/12/28 06:00 [medline] PHST- 2021/10/31 21:15 [entrez] PHST- 2021/10/30 00:00 [pmc-release] AID - 6414599 [pii] AID - gkab983 [pii] AID - 10.1093/nar/gkab983 [doi] PST - ppublish SO - Nucleic Acids Res. 2021 Nov 18;49(20):11920-11937. doi: 10.1093/nar/gkab983.