Expression Pattern and Splicing Function of Mouse ZNF265

Li, Jing; Chen, Xianhua; Xiao, Ping-Jie; Li, Li; Wang, Lin; Huang, Jia; Xu, Ping

doi:10.1007/s11064-007-9461-3

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…It has been demonstrated that ZRANB2 can alter the splicing of Tra2-␤, GLUR-B, and SMN2 reporter genes in splicing assays (6,7). The Tra2-␤ reporter gene contains 4 exons (Fig.…”

Section: The Binding Preferences Of Zranb2 Corroborate Functional Splmentioning

confidence: 99%

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The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5′ splice site-like sequences

Loughlin

Mansfield

Vaz

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA (Nx)AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5 splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine ''ladder.'' A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.protein structure ͉ RanBP2 zinc fingers ͉ RNA-binding proteins ͉ splicing A lmost all human genes are thought to be alternatively spliced, and it has been estimated that at least 15% of human diseases are associated with changes in RNA processing (1). The selection of splice sites is influenced heavily by the binding of accessory splicing factors to regulatory sequences in the pre-mRNA. SR proteins are splicing factors that contain a C-terminal Arg/Ser-rich (RS) domain and either 1 or 2 N-terminal RNA recognition motifs (RRMs) (2). They play crucial roles in constitutive and alternative splicing, promoting recognition of splice sites by binding to exonic splicing enhancers (ESEs). RRM domains bind ssRNA with high affinity in a sequence-specific manner, whereas RS domains appear to facilitate both protein-protein and protein-RNA interactions (3, 4). Other RS domain-containing proteins that lack a canonical RRM, termed ''SR-like'' proteins (see, for example, ref. 5) are also known to play roles in splicing.ZRANB2 (Zis, ZNF265) is an SR-like nuclear protein that is expressed in most tissues and is conserved between nematodes and mammals. It interacts with the spliceosomal proteins U1-70K and U2AF 35 and can alter the distribution of splice variants of GluR-B, SMN2, and Tra2␤ in minigene reporter assays (6, 7). As such, ZRANB2 appears to regulate splice site choice. However, in place of the canonical RNA-binding RRM domains, ZRANB2 displays 2 N-terminal RanBP2-type zinc fingers (ZnFs).RanBP2-type ZnF domains are defined by the consensus sequence W-X-C-X 2-4 -C-X 3 -N-X 6 -C-X 2 -C. They occur multiple times in at least 21 human proteins, and the fold comprises 2 distorted ␤-hairpins sandwiching a central tryptophan residue and ...

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“…It has been demonstrated that ZRANB2 can alter the splicing of Tra2-␤, GLUR-B, and SMN2 reporter genes in splicing assays (6,7). The Tra2-␤ reporter gene contains 4 exons (Fig.…”

Section: The Binding Preferences Of Zranb2 Corroborate Functional Splmentioning

confidence: 99%

“…It interacts with the spliceosomal proteins U1-70K and U2AF 35 and can alter the distribution of splice variants of GluR-B, SMN2, and Tra2␤ in minigene reporter assays (6,7). As such, ZRANB2 appears to regulate splice site choice.…”

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confidence: 99%

The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5′ splice site-like sequences

Loughlin

Mansfield

Vaz

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…ZRANB2 contains 2 zinc finger domains, a C-terminal RS (arginine/serine-rich) domain, a glutamic acid-rich domain, and a nuclear localization sequence [4]. It interacts with components of the splicing factors U170K , U2AF35 , and XE7 and regulates splicing of GluR-B , SMN2 , and Tra2 β [5–7]. The 2 zinc finger domains recognize single-stranded RNA (ssRNA) and bind to a consensus AGGUAA motif [8].…”

Section: Introductionmentioning

confidence: 99%

Intron Retention and TE Exonization Events inZRANB2

Park

Huh

Kim

et al. 2012

Comparative and Functional Genomics

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The Zinc finger, RAN-binding domain-containing protein 2 (ZRANB2), contains arginine/serine-rich (RS) domains that mediate its function in the regulation of alternative splicing. The ZRANB2 gene contains 2 LINE elements (L3b, Plat_L3) between the 9th and 10th exons. We identified the exonization event of a LINE element (Plat_L3). Using genomic PCR, RT-PCR amplification, and sequencing of primate DNA and RNA samples, we analyzed the evolutionary features of ZRANB2 transcripts. The results indicated that 2 of the LINE elements were integrated in human and all of the tested primate samples (hominoids: 3 species; Old World monkey: 8 species; New World monkey: 6 species; prosimian: 1 species). Human, rhesus monkey, crab-eating monkey, African-green monkey, and marmoset harbor the exon derived from LINE element (Plat_L3). RT-PCR amplification revealed the long transcripts and their differential expression patterns. Intriguingly, these long transcripts were abundantly expressed in Old World monkey lineages (rhesus, crab-eating, and African-green monkeys) and were expressed via intron retention (IR). Thus, the ZRANB2 gene produces 3 transcript variants in which the Cterminus varies by transposable elements (TEs) exonization and IR mechanisms. Therefore, ZRANB2 is valuable for investigating the evolutionary mechanisms of TE exonization and IR during primate evolution.

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“…Studies show that ZNF265 proteins are co-immunoprecipitated with mRNAs and colocalize with splicing factors SMN, U1-70K, U2AF35 and SC35, indicating that ZNF265 is a novel component of spliceosomes (11,12). It has been known that many zinc finger proteins such as Gfi, GATA3, Egr-1, Aiolos, ZNF569 (13,14) play a crucial role in the immunoregulatory function of animals.…”

Section: Introductionmentioning

confidence: 99%