Understanding RNA Binding by the Nonclassical Zinc Finger Protein CPSF30, a Key Factor in Polyadenylation during Pre-mRNA Processing

Biochemistry ◽  
2021 ◽  
Author(s):  
Jordan D. Pritts ◽  
Abdulafeez A. Oluyadi ◽  
Weiliang Huang ◽  
Geoffrey D. Shimberg ◽  
Maureen A. Kane ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Mrna Processing ◽  
Finger Protein ◽  
Key Factor

Zinc finger protein ZFP36L1 inhibits flavivirus infection by both 5′-3′ XRN1 and 3′-5′ RNA-exosome RNA decay pathways.

2021 ◽  
Author(s):  
Han Chiu ◽  
Hsin-Ping Chiu ◽  
Han-Pang Yu ◽  
Li-Hsiung Lin ◽  
Zih-Ping Chen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Viral Rna ◽  
Rna Decay ◽  
Finger Protein ◽  
Zinc Finger Motifs ◽  
Rna Exosome

Zinc-finger protein 36, CCCH type-like 1 (ZFP36L1), containing tandem CCCH-type zinc-finger motifs with an RNA-binding property, plays an important role in cellular RNA metabolism mainly via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 has potent antiviral activity against influenza A virus infection. However, its role in the host defense response against flaviviruses has not been addressed. Here, we demonstrate that ZFP36L1 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L1 reduced JEV and DENV infection, and ZFP36L1 knockdown enhanced viral replication. ZFP36L1 destabilized the JEV genome by targeting and degrading viral RNA mediated by both 5′-3′ XRN1 and 3′-5′ RNA-exosome RNA decay pathways. Mutation in both zinc-finger motifs of ZFP36L1 disrupted RNA-binding and antiviral activity. Furthermore, the viral RNA sequences specifically recognized by ZFP36L1 were mapped to the 3'-untranslated region of the JEV genome with the AU-rich element (AUUUA) motif. We extend the function of ZFP36L1 to host antiviral defense by directly binding and destabilizing the viral genome via recruiting cellular mRNA decay machineries. Importance Cellular RNA-binding proteins are among the first lines of defense against various viruses, particularly RNA viruses. ZFP36L1 belongs to the CCCH-type zinc-finger protein family and has RNA-binding activity; it has been reported to directly bind to the AU-rich elements (AREs) of a subset of cellular mRNAs and then lead to mRNA decay by recruiting mRNA degrading enzymes. However, the antiviral potential of ZFP36L1 against flaviviruses has not yet been fully demonstrated. Here, we reveal the antiviral potential of human ZFP36L1 against Japanese encephalitis virus (JEV) and dengue virus (DENV). ZFP36L1 specifically targeted the ARE motif within viral RNA and triggered the degradation of viral RNA transcripts via cellular degrading enzymes, 5′-3′ XRN1 and 3′-5′ RNA exosome. These findings provide mechanistic insights into how human ZFP36L1 serves as a host antiviral factor to restrict flavivirus replication.

scholarly journals The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1539 ◽  
Author(s):  
Yogesh Saini ◽  
Jian Chen ◽  
Sonika Patial
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Zinc Finger ◽  
Binding Proteins ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Finger Protein ◽  
Post Transcriptional Regulation

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.

scholarly journals Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt

2015 ◽  
Vol 29 (5) ◽  
pp. 501-512 ◽  
Author(s):  
Jernej Murn ◽  
Kathi Zarnack ◽  
Yawei J. Yang ◽  
Omer Durak ◽  
Elisabeth A. Murphy ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Neuronal Morphology ◽  
Finger Protein

scholarly journals Unraveling the RNA Binding Properties of the Iron–Sulfur Zinc Finger Protein CPSF30

Biochemistry ◽  
2020 ◽  
Vol 59 (8) ◽  
pp. 970-982
Author(s):  
Jordan D. Pritts ◽  
Matthew S. Hursey ◽  
Jamie L. Michalek ◽  
Sharon Batelu ◽  
Timothy L. Stemmler ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Binding Properties ◽  
Iron Sulfur ◽  
Finger Protein

scholarly journals Structure, expression and in vitro functional characterization of a novel RNA binding zinc finger protein from Xenopus.

1991 ◽  
Vol 10 (10) ◽  
pp. 3087-3093 ◽  
Author(s):  
M. Köster ◽  
U. Kühn ◽  
T. Bouwmeester ◽  
W. Nietfeld ◽  
T. el-Baradi ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Functional Characterization ◽  
Finger Protein

scholarly journals Tristetraprolin and Its Family Members Can Promote the Cell-Free Deadenylation of AU-Rich Element-Containing mRNAs by Poly(A) Ribonuclease

2003 ◽  
Vol 23 (11) ◽  
pp. 3798-3812 ◽  
Author(s):  
Wi S. Lai ◽  
Elizabeth A. Kennington ◽  
Perry J. Blackshear
Keyword(s):  
Zinc Finger ◽  
Mrna Stability ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Family Members ◽  
Intact Cells ◽  
Free System ◽  
Finger Protein ◽  
A Cell ◽  
Related Proteins

ABSTRACT Eukaryotic mRNA stability can be influenced by AU-rich elements (AREs) within mRNA primary sequences. Tristetraprolin (TTP) is a CCCH tandem zinc finger protein that binds to ARE-containing transcripts and destabilizes them, apparently by first promoting the removal of their poly(A) tails. We developed a cell-free system in which TTP and its related proteins stimulated the deadenylation of ARE-containing, polyadenylated transcripts. Transcript deadenylation was not stimulated when a mutant TTP protein was used that was incapable of RNA binding, nor when a mutant ARE was present that did not bind TTP. The ability of TTP to promote transcript deadenylation required Mg2+, but not ATP or prior capping of the RNA substrate. Cotransfection and additivity studies with the poly(A) RNase (PARN) demonstrated that TTP promoted the ability of this enzyme to deadenylate ARE-containing, polyadenylated transcripts, while having no effect on transcripts lacking an ARE. There was no effect of TTP to act synergistically with enzymatically inactive PARN mutants. We conclude that TTP can promote the deadenylation of ARE-containing, polyadenylated substrates by PARN. This interaction may be responsible for the ability of TTP and its family members to promote the deadenylation of such transcripts in intact cells.

scholarly journals Zinc finger protein ZFP36L1 inhibits influenza A virus through translational repression by targeting HA, M and NS RNA transcripts

2020 ◽  
Author(s):  
Ren-Jye Lin ◽  
Chih-Heng Huang ◽  
Ping-Cheng Liu ◽  
I-Chieh Lin ◽  
Yu-Ling Huang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Zinc Finger ◽  
Influenza A ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Protein Translation ◽  
Translational Repression ◽  
Ns1 Protein ◽  
Innate Defense ◽  
Finger Protein

Abstract ZFP36L1, a CCCH-type zinc finger protein, is an RNA-binding protein that participates in controlling cellular mRNA abundance and turnover by posttranscriptional regulation. Here, we demonstrated that ZFP36L1 has an important role in host defense against influenza A virus (IAV) infection. Overexpression of ZFP36L1 reduced IAV replication via translational repression of HA, M and NS RNA segment transcripts. IAV infection upregulated cellular ZFP36L1 expression, and endogenous ZFP36L1 knockdown significantly enhanced IAV replication. ZFP36L1 directly binds to IAV NS1 mRNA in the cytoplasm and blocks the expression and function of NS1 protein. Mutation of CCCH-type zinc finger domains of ZFP36L1 lost its antiviral potential and NS1 mRNA binding. Thus, ZFP36L1 can act as a host innate defense by targeting HA, M and NS mRNA transcripts to suppress viral protein translation.

Sign in / Sign up

Export Citation Format

Share Document