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Titolo:
Alternative promoter usage and splicing of ZNF74 multifinger gene produce protein isoforms with a different repressor activity and nuclear partitioning
Autore:
Cote, F; Boisvert, FM; Grondin, B; Bazinet, H; Goodyer, CG; Bazett-Jones, DP; Aubry, M;
Indirizzi:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal Montreal PQ Canada H3C 3J7 im, Montreal, PQ H3C 3J7, Canada McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada McGill Univ Montreal PQ Canada H3A 2T5 diat, Montreal, PQ H3A 2T5, Canada Univ Calgary, Fac Med, Dept Cell Biol & Anat, Calgary, AB, Canada Univ Calgary Calgary AB Canada ept Cell Biol & Anat, Calgary, AB, Canada
Titolo Testata:
DNA AND CELL BIOLOGY
fascicolo: 3, volume: 20, anno: 2001,
pagine: 159 - 173
SICI:
1044-5498(200103)20:3<159:APUASO>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ZINC-FINGER PROTEINS; RNA-POLYMERASE-II; MESSENGER-RNA; TRANSCRIPTIONAL REPRESSION; DIGEORGE-SYNDROME; SC-35 DOMAINS; WT1; ORGANIZATION; BINDING; DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Aubry, M Univ Montreal, Dept Biochim, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada Univ Montreal CP 6128,Succursale Ctr Ville Montreal PQ Canada H3C 3J7
Citazione:
F. Cote et al., "Alternative promoter usage and splicing of ZNF74 multifinger gene produce protein isoforms with a different repressor activity and nuclear partitioning", DNA CELL B, 20(3), 2001, pp. 159-173

Abstract

We have previously shown that ZNF74, a candidate gene for DiGeorge syndrome, encodes a developmentally expressed zinc finger gene of the Kruppel-associated box (KRAB) multifinger subfamily. Using RACE, RT-PCR, and primer extension on human fetal brain and heart mRNAs, we here demonstrate the existence of six mRNA variants resulting from alternative promoter usage and splicing. These transcripts encode four protein isoforms differing at their N terminus by the composition of their KRAB motif. One isoform, ZNF74-I, whichcorresponds to the originally cloned cDNA, was found to be encoded by two additional mRNA variants. This isoform, which contains a KRAB motif lackingthe N terminus of the KRAB A box, was devoid of transcriptional activity. In contrast, ZNF74-II, a newly identified form of the protein that is encoded by a single transcript and contains an intact KRAB domain with full A and B boxes, showed strong repressor activity. Deconvolution immunofluorescence microscopy using transfected human neuroblastoma cells and nonimmortalized HS68 fibroblasts revealed a distinct subcellular distribution for ZNF74-I and ZNF74-II, In contrast to ZNF74-I, which largely colocalizes with SC-35 in nuclear speckles enriched in splicing factors, the transcriptionally active ZNF74-II had a more diffuse nuclear distribution that is more characteristic of transcriptional regulators. Taken with the previously described RNA-binding activity of ZNP74-I and direct interaction with a hyperphosphorylated form of the RNA polymerase IT participating in pre-mRNA processing, our results suggest that the two ZNF74 isoforms exert different or complementary roles in RNA maturation and in transcriptional regulation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 05:53:38