The U2AF35-related protein Urp contacts the 3′ splice site to promote U12-type intron splicing and the second step of U2-type intron splicing

Shen, Haihong; Zheng, Xuexiu; Luecke, Stephan; Green, Michael R.

doi:10.1101/gad.1974810

Cited by 97 publications

(99 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the U2AF 35 mutations alter specific ZnK residues, whereas the URP mutations are randomly distributed throughout the protein sequence and often null. This difference most likely reflects the distinct functions of the two proteins: U2AF 35 recognizes the intron-exon junction of the major class of splice sites in conjunction with U2AF 65 (Merendino et al 1999;Wu et al 1999;Zorio and Blumenthal 1999), as opposed to a selective role for URP in a "minor," stress-associated class of intron splicing (Shen et al 2010;Madan et al 2015). Yet, no U2AF 65 paralog has been identified as a ULM partner for the URP UHM to date.…”

Section: Do Uhms Bind Rna?mentioning

confidence: 99%

Unmasking the U2AF homology motif family: a bona fide protein–protein interaction motif in disguise

Loerch

Kielkopf

2016

RNA

View full text Add to dashboard Cite

U2AF homology motifs (UHM) that recognize U2AF ligand motifs (ULM) are an emerging family of protein-protein interaction modules. UHM-ULM interactions recur in pre-mRNA splicing factors including U2AF1 and SF3b1, which are frequently mutated in myelodysplastic syndromes. The core topology of the UHM resembles an RNA recognition motif and is often mistakenly classified within this large family. Here, we unmask the charade and review recent discoveries of UHM-ULM modules for protein-protein interactions. Diverse polypeptide extensions and selective phosphorylation of UHM and ULM family members offer new molecular mechanisms for the assembly of specific partners in the early-stage spliceosome.

show abstract

Section: Do Uhms Bind Rna?mentioning

confidence: 99%

Unmasking the U2AF homology motif family: a bona fide protein–protein interaction motif in disguise

Loerch

Kielkopf

2016

RNA

View full text Add to dashboard Cite

show abstract

“…In human cells, URP participates in both U2 and U12 splicing and is essential for cell culture survival (Tronchè re et al, 1997; Shen et al, 2010). The viability of rgh3 endosperm cells in culture suggests the rgh3-umu1 hypomorph allele does not disrupt core splicing functions.…”

Section: Rgh3 Is Required For a Subset Of Rna Splicing Eventsmentioning

confidence: 99%

“…The predicted RGH3 protein is homologous to human U2AF 35 Related Protein (URP). URP is involved in RNA splicing of both U2 and U12 introns in mammals (Tronchè re et al, 1997;Shen et al, 2010). We amplified, cloned, and sequenced 45 independent Rgh3 RT-PCR products.…”

Section: Rgh3 Encodes a Predicted Rna Splicing Factormentioning

confidence: 99%

See 1 more Smart Citation

MaizeRough Endosperm3Encodes an RNA Splicing Factor Required for Endosperm Cell Differentiation and Has a Nonautonomous Effect on Embryo Development

et al. 2011

View full text Add to dashboard Cite

Endosperm and embryo development are coordinated via epigenetic regulation and signaling between these tissues. In maize (Zea mays), the endosperm-embryo signals are not known, but endosperm cellularization is a key event for embryos to form shoots and roots. We screened seed mutants for nonautonomous functions in endosperm and embryo development with genetically nonconcordant seeds and identified the recessive mutant rough endosperm3 (rgh3). The wild-type Rgh3 allele is required in the endosperm for embryos to develop and has an autonomous role in embryo and seedling development. Endosperm cell differentiation is defective in rgh3. Results from endosperm cell culture indicate that rgh3 mutants remain in a proliferative state through mid-seed development. Rgh3 encodes the maize U2AF 35 Related Protein (URP), an RNA splicing factor involved in both U2 and U12 splicing. The Rgh3 allele produces at least 19 alternative splice variants with only one isoform encoding a full-length ortholog to URP. The full-length RGH3a isoform localizes to the nucleolus and displays a speckled pattern within the nucleoplasm, and RGH3a colocalizes with U2AF 65 . A survey of alternatively spliced transcripts found that, in the rgh3 mutant, a fraction of noncanonical splicing events are altered. Our findings suggest that differentiation of maize endosperm cell types is necessary for embryos to develop. The molecular cloning of Rgh3 suggests that alternative RNA splicing is needed for cell differentiation, development, and plant viability.

show abstract

“…Alternative splicing contributes to protein diversity. In alternative splicing, different 5' splice-sites or 3' splice-sites are selected to induce exon inclusion or skipping (3,4). Inclusion/skipping of exons are regulated by cis-acting or trans-acting elements (5,6).…”

Section: Introductionmentioning

confidence: 99%

CD44 alternative splicing and hnRNP A1 expression are associated with the metastasis of breast cancer

et al. 2015

Self Cite

View full text Add to dashboard Cite

Abstract. CD44 is a transmembrane receptor for hyaluronic acid. CD44 pre-mRNA contains 19 exons, 9 of which are alternatively spliced. Among the CD44 spliced variants, the v4-7 variant, one of the v6 exon-containing isoforms that contains variable exon 4, 5, 6 and 7, confers metastatic potential to nonmetastatic cells. Splicing of CD44 and the function of CD44 isoforms are different in breast cancer cells. hnRNP A1 is a ubiquitously expressed protein with an inhibitory function in pre-mRNA splicing. We showed that CD44v6 isoform, which includes all of the v6-containing mRNA isoforms, had the highest expression level in non-metatatic breast cancer cells (MCF7) when compared to the level in metastatic breast cancer cells (MDA-MB-231) and normal breast cells (MCF10A). Furthermore we showed that hnRNP A1 knockdown regulated splicing of CD44 differently in breast cancer cells. We showed here that CD44 isoform expression is completely different in MDA-MB-231 cells than that in MCF7 and MCF10A cells, whereas MCF7 and MCF10A cells had a similar expression pattern of CD44 isoforms. RT-PCR analysis of CD44v6 showed that MCF7 and MCF10A cells predominantly expressed the c5v6v7v8v9v10c6 isoform. However, in addition to this isoform, MDA-MB-231 cells also expressed the c5v6v8v9v10c6 and c5v6c6 isoforms. We also found that knockdown of hnRNP A1 significantly reduced the expression of c5v6v7v8v9v10c6 and c5v6v8v9v10c6, and promoted the expression of c5v6c6. hnRNP A1 knockdown significantly induced cell death. In addition, hnRNP A1 knockdown induced a decrease in cell invasion in the MDA-MB-231 cells. Our results indicate that the knockdown of hnRNP A1 has a specific function on the splicing of CD44 in breast cancer cells.

show abstract

The U2AF35-related protein Urp contacts the 3′ splice site to promote U12-type intron splicing and the second step of U2-type intron splicing

Cited by 97 publications

References 29 publications

Unmasking the U2AF homology motif family: a bona fide protein–protein interaction motif in disguise

Unmasking the U2AF homology motif family: a bona fide protein–protein interaction motif in disguise

MaizeRough Endosperm3Encodes an RNA Splicing Factor Required for Endosperm Cell Differentiation and Has a Nonautonomous Effect on Embryo Development

CD44 alternative splicing and hnRNP A1 expression are associated with the metastasis of breast cancer

Contact Info

Product

Resources

About