The essential splicing factor U2AF (U2 auxiliary factor) is a heterodimer composed of 65-kDa (U2AF(65)) and 35-kDa (U2AF(35)) subunits. U2AF(35) has multiple functions in pre-mRNA splicing. First, U2AF(35) has been shown to function by directly interacting with the AG at the 3' splice site. Second, U2AF(35) is thought to play a role in the recruitment of U2AF(65) by serine-arginine-rich (SR) proteins in enhancer-dependent splicing. It has been proposed that the physical interaction between the arginine-serine-rich (RS) domain of U2AF(35) and SR proteins is important for this activity. However, other data suggest that this may not be the case. Here, we report the identification of a mammalian gene that encodes a 26-kDa protein bearing strong sequence similarity to U2AF(35), designated U2AF(26). The N-terminal 187 amino acids of U2AF(35) and U2AF(26) are nearly identical. However, the C-terminal domain of U2AF(26) lacks many characteristics of the U2AF(35) RS domain and, therefore, might be incapable of interacting with SR proteins. We show that U2AF(26) can associate with U2AF(65) and can functionally substitute for U2AF(35) in both constitutive and enhancer-dependent splicing, demonstrating that the RS domain of the small U2AF subunit is not required for splicing enhancer function. Finally, we show that U2AF(26) functions by enhancing the binding of U2AF(65) to weak 3' splice sites. These studies identify U2AF(26) as a mammalian splicing factor and demonstrate that distinct U2AF complexes can participate in pre-mRNA splicing. Based on its sequence and functional similarity to U2AF(35), U2AF(26) may play a role in regulating alternative splicing.
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http://dx.doi.org/10.1128/MCB.22.1.221-230.2002 | DOI Listing |
Chromosome Res
January 2025
Saint-Petersburg State University, Saint-Petersburg, Russia.
Danio rerio, commonly known as zebrafish, is an established model organism for the developmental and cell biology studies. Although significant progress has been made in the analysis of the D. rerio genome, cytogenetic studies face challenges due to the unclear identification of chromosomes.
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January 2025
Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University Hospital, 14004 Cordoba, Spain.
Alternative splicing is a post-transcriptional process resulting in multiple protein isoforms from a single gene. Abnormal splicing may lead to metabolic diseases, including type 2 diabetes mellitus (T2DM). To identify the splicing factor expression that predicts T2DM remission in coronary heart disease (CHD) patients, we identified newly diagnosed T2DM at baseline ( = 190) from the CORDIOPREV study.
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January 2025
European Molecular Biology Laboratory (EMBL), EMBL Grenoble, 71 Avenue des Martyrs, 38042 Grenoble, France. Electronic address:
The minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying molecular mechanisms remain elusive. Here, we report a cryoelectron microscopy (cryo-EM) reconstruction of the 13-subunit human U11 small nuclear ribonucleoprotein particle (snRNP) complex in apo and substrate-bound forms, revealing the architecture of the U11 small nuclear RNA (snRNA), five minor spliceosome-specific factors, and the mechanism of the U12-type 5' splice site (5'SS) recognition.
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January 2025
Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Shanghai Integration and Innovation Center of Marine Medical Engineering, China. Electronic address:
The identification of novel molecular candidates capable of treating osteoarthritis (OA) has significant clinical implications. Monocyte locomotion inhibitory factor peptide (MLIF) is a pentapeptide derived from Entamoeba histolytica. It has been found possesses selective anti-inflammatory effects both in vitro and in vivo.
View Article and Find Full Text PDFRNA
January 2025
MRC University of Glasgow Centre for Virus Research, University of Glasgow.
Cytoplasmic viruses interact intricately with the nuclear pore complex and nuclear import/export machineries, affecting nuclear-cytoplasmic trafficking. This can lead to the selective accumulation of nuclear RNA-binding proteins (RBPs) in the cytoplasm. Pioneering research has shown that relocated RBPs serve as an intrinsic defence mechanism against viruses, which involves RNA export, splicing and nucleolar factors.
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