A conserved CCCH-type zinc finger protein regulates mRNA nuclear adenylation and export

Coupling of messenger RNA (mRNA) nuclear export with prior processing steps aids in the fidelity and efficiency of mRNA transport to the cytoplasm. In this study, we show that the processes of export and polyadenylation are coupled via the Drosophila melanogaster CCCH-type zinc finger protein CG6694/dZC3H3 through both physical and functional interactions. We show that depletion of dZC3H3 from S2R+ cells results in transcript hyperadenylation. Using targeted coimmunoprecipitation and liquid chromatography mass spectrometry (MS)/MS techniques, we characterize interactions of known components of the mRNA nuclear export and polyadenylation machineries with dZC3H3. Furthermore, we demonstrate the functional conservation of this factor, as depletion of its human homologue ZC3H3 by small interfering RNA results in an mRNA export defect in human cells as well. Nuclear polyadenylated (poly(A)) RNA in ZC3H3-depleted cells is sequestered in foci removed from SC35-containing speckles, indicating a shift from the normal subnuclear distribution of poly(A) RNA. Our data suggest a model wherein ZC3H3 interfaces between the polyadenylation machinery, newly poly(A) mRNAs, and factors for transcript export.

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An evolutionary conserved zinc finger protein is involved inToxoplasma gondiimRNA nuclear export

Cellular Microbiology ◽

10.1111/cmi.12644 ◽

2016 ◽

Vol 19 (2) ◽

pp. e12644 ◽

Cited By ~ 7

Author(s):

Mathieu Gissot ◽

Agnès Hovasse ◽

Laurent Chaloin ◽

Christine Schaeffer-Reiss ◽

Alain Van Dorsselaer ◽

...

Keyword(s):

Zinc Finger ◽

Nuclear Export ◽

Zinc Finger Protein ◽

Finger Protein

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Design of a synthetic luminescent probe from a biomolecule binding domain: selective detection of AU-rich mRNA sequences

Chemical Science ◽

10.1039/c6sc04086a ◽

2017 ◽

Vol 8 (2) ◽

pp. 1658-1664 ◽

Cited By ~ 6

Author(s):

Laurent Raibaut ◽

William Vasseur ◽

Geoffrey D. Shimberg ◽

Christine Saint-Pierre ◽

Jean-Luc Ravanat ◽

...

Keyword(s):

Zinc Finger ◽

Messenger Rna ◽

Untranslated Region ◽

Zinc Finger Protein ◽

Binding Domain ◽

Selective Detection ◽

Luminescent Probe ◽

Time Resolved ◽

Luminescent Sensor ◽

Finger Protein

We report the design of a luminescent sensor based upon the zinc finger protein TIS11d, that allows for the selective time-resolved detection of the UUAUUUAUU sequence of the 3′-untranslated region of messenger RNA.

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Isolation of a cDNA clone encoding a zinc finger protein highly expressed in T-leukemia lines

Blood ◽

10.1182/blood.v80.10.2571.2571 ◽

1992 ◽

Vol 80 (10) ◽

pp. 2571-2576 ◽

Cited By ~ 3

Author(s):

BY Wu ◽

EW Hanley ◽

LA Turka ◽

GJ Nabel

Keyword(s):

Zinc Finger ◽

Cdna Clone ◽

Messenger Rna ◽

Zinc Finger Protein ◽

Leukemia Cell ◽

Lymphoid Cells ◽

Gap Gene ◽

Finger Protein ◽

Leukemia Cell Lines

Abstract A cDNA clone encoding a novel zinc finger protein expressed in lymphoid cells has been isolated. This protein contains 5 repeats of the C2H2 motif previously described in the Drosophila gap gene, Kruppel, which is involved in embryo segmentation. Northern blot analysis showed that the messenger RNA (mRNA) encoding this protein is expressed at high levels in a variety of T-leukemia cell lines, at lower levels in some B cells, but is not observed in nonlymphoid cells. Within the T lineage, the mRNA is found at high levels in both alpha beta and gamma delta T cells. These data suggest that this cDNA, designated Hkr-T1, represents a gene that may contribute to the determination of the differentiation and the specificity within lymphoid cells.

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Persistent repression of tau in the brain using engineered zinc finger protein transcription factors

Science Advances ◽

10.1126/sciadv.abe1611 ◽

2021 ◽

Vol 7 (12) ◽

pp. eabe1611

Author(s):

Susanne Wegmann ◽

Sarah L. DeVos ◽

Bryan Zeitler ◽

Kimberly Marlen ◽

Rachel E. Bennett ◽

...

Keyword(s):

Transcription Factors ◽

Zinc Finger ◽

Messenger Rna ◽

Zinc Finger Protein ◽

Neuronal Damage ◽

Brain Diseases ◽

Transcriptional Level ◽

Finger Protein ◽

Model Of Alzheimer’S Disease ◽

Protein Transcription

Neuronal tau reduction confers resilience against β-amyloid and tau-related neurotoxicity in vitro and in vivo. Here, we introduce a novel translational approach to lower expression of the tau gene MAPT at the transcriptional level using gene-silencing zinc finger protein transcription factors (ZFP-TFs). Following a single administration of adeno-associated virus (AAV), either locally into the hippocampus or intravenously to enable whole-brain transduction, we selectively reduced tau messenger RNA and protein by 50 to 80% out to 11 months, the longest time point studied. Sustained tau lowering was achieved without detectable off-target effects, overt histopathological changes, or molecular alterations. Tau reduction with AAV ZFP-TFs was able to rescue neuronal damage around amyloid plaques in a mouse model of Alzheimer’s disease (APP/PS1 line). The highly specific, durable, and controlled knockdown of endogenous tau makes AAV-delivered ZFP-TFs a promising approach for the treatment of tau-related human brain diseases.

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Isolation of a cDNA clone encoding a zinc finger protein highly expressed in T-leukemia lines

Blood ◽

10.1182/blood.v80.10.2571.bloodjournal80102571 ◽

1992 ◽

Vol 80 (10) ◽

pp. 2571-2576

Author(s):

BY Wu ◽

EW Hanley ◽

LA Turka ◽

GJ Nabel

Keyword(s):

Zinc Finger ◽

Cdna Clone ◽

Messenger Rna ◽

Zinc Finger Protein ◽

Leukemia Cell ◽

Lymphoid Cells ◽

Gap Gene ◽

Finger Protein ◽

Leukemia Cell Lines

A cDNA clone encoding a novel zinc finger protein expressed in lymphoid cells has been isolated. This protein contains 5 repeats of the C2H2 motif previously described in the Drosophila gap gene, Kruppel, which is involved in embryo segmentation. Northern blot analysis showed that the messenger RNA (mRNA) encoding this protein is expressed at high levels in a variety of T-leukemia cell lines, at lower levels in some B cells, but is not observed in nonlymphoid cells. Within the T lineage, the mRNA is found at high levels in both alpha beta and gamma delta T cells. These data suggest that this cDNA, designated Hkr-T1, represents a gene that may contribute to the determination of the differentiation and the specificity within lymphoid cells.

Download Full-text