Splicing and beyond: The many faces of the Prp19 complex

Chanarat, Sittinan; Sträßer, Katja

doi:10.1016/j.bbamcr.2013.05.023

Cited by 128 publications

(127 citation statements)

References 92 publications

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“…Intriguingly, among the proteins that interact with Prp8, our MS results identified a set of splicing factors, which form the Prp19 complex (Prp19C), also known as NTC (21,31,32). Compared with Col, the atprmt5 mutants showed significantly reduced normalized spectral counts from the Prp19C/NTC core proteins, including MAC3A and MAC3B (human Prp19 homolog in Arabidopsis), MOS4 (human SPF27 homolog in Arabidopsis), CDC5, and PRL1, and the Prp19C/NTC-associated proteins (SYF1, AQR, CRN1c, SKIP, ECM2, ISY1, and PPI) (Fig.…”

Section: The Suppressors Partially Rescue the Splicing Alterations Ofmentioning

confidence: 99%

“…A preformed U4/U6.U5 tri-snRNP, in which the U4 and U6 snRNAs are basepaired, joins the prespliceosome to form the precatalytic spliceosome. A large structural rearrangement occurs to form an active spliceosome, involving the unwinding of U4/U6 base pairing interaction, the release of U1 and U4 snRNAs, and the addition of a non-snRNP protein complex called the Prp19 complex (Prp19C) or the NineTeen Complex (NTC) (21). Then the branch-point adenosine residue nucleophilically attacks the 5′ splice site for the first transesterification reaction, followed by the second transesterification reaction, resulting in the ligation of two exons.…”

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confidence: 99%

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Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5

Deng

Wang

et al. 2016

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

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Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is involved in a multitude of biological processes in eukaryotes. Symmetric arginine dimethylation mediated by PRMT5 modulates constitutive and alternative pre-mRNA splicing of diverse genes to regulate normal growth and development in multiple species; however, the underlying molecular mechanism remains largely unknown. A genetic screen for suppressors of an Arabidopsis symmetric arginine dimethyltransferase mutant, atprmt5, identified two gain-of-function alleles of pre-mRNA processing factor 8 gene (prp8-8 and prp8-9), the highly conserved core component of the U5 small nuclear ribonucleoprotein (snRNP) and the spliceosome. These two atprmt5 prp8 double mutants showed suppression of the developmental and splicing alterations of atprmt5 mutants. In atprmt5 mutants, the NineTeen complex failed to be assembled into the U5 snRNP to form an activated spliceosome; this phenotype was restored in the atprmt5 prp8-8 double mutants. We also found that loss of symmetric arginine dimethylation of Sm proteins prevents recruitment of the NineTeen complex and initiation of spliceosome activation. Together, our findings demonstrate that symmetric arginine dimethylation has important functions in spliceosome assembly and activation, and uncover a key molecular mechanism for arginine methylation in pre-mRNA splicing that impacts diverse developmental processes.arginine methylation | protein arginine methyltransferase | AtPRMT5 | pre-mRNA splicing | Prp19C/NTC P rotein arginine methyltransferase 5 (PRMT5), a highly conserved type II protein arginine methyltransferase, transfers methyl groups to arginine residues, generating monomethylarginine and symmetric ω-N G , N′ G -dimethylarginine (SDMA) (1-3). In mammals, PRMT5 methylates and interacts with diverse proteins, including histones and other proteins, and has long been implicated in the modulation of a variety of processes, such as transcriptional regulation, RNA metabolism (4), apoptosis (5), signal transduction (6), and germ cell development (7). Both loss-of-function and overexpression of PRMT5 are fatal in mammals (8). AtPRMT5, the Arabidopsis homolog of PRMT5, regulates multiple aspects of plant growth and development, such as flowering time, growth rate, leaf morphology, sensitivity to stress conditions, and circadian rhythm, by modulating transcription, constitutive and alternative precursor mRNA (pre-mRNA) splicing of diverse genes (9-13). AtPRMT5 also mediates the symmetric arginine dimethylation of uridine-rich small nuclear ribonucleoproteins (U snRNPs) AtSmD1, D3, and AtLSm4 proteins, thus linking arginine methylation and splicing (10,11,13). However, the exact mechanism remains elusive.Pre-mRNA splicing occurs in the nucleus, removing introns and ligating exons (14). In eukaryotes, most introns are spliced in a series of reactions catalyzed by the spliceosome, which consists of five subcomplexes of U snRNPs and several non-snRNP factors. Each U snRNP contains distinct splicing...

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Section: The Suppressors Partially Rescue the Splicing Alterations Ofmentioning

confidence: 99%

mentioning

confidence: 99%

Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5

Deng

Wang

et al. 2016

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

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“…Bud31 has been shown to be required for efficient progression to the first step of splicing (32). The paucity of NTC proteins in C. merolae is particularly unexpected, given that this complex has been implicated in a wide range of processes outside of splicing, including transcription and mRNA export (38).…”

Section: Discussionmentioning

confidence: 99%

Dramatically reduced spliceosome in Cyanidioschyzon merolae

Stark

Dunn²,

Dunn

et al. 2015

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

143

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The human spliceosome is a large ribonucleoprotein complex that catalyzes pre-mRNA splicing. It consists of five snRNAs and more than 200 proteins. Because of this complexity, much work has focused on the Saccharomyces cerevisiae spliceosome, viewed as a highly simplified system with fewer than half as many splicing factors as humans. Nevertheless, it has been difficult to ascribe a mechanistic function to individual splicing factors or even to discern which are critical for catalyzing the splicing reaction. We have identified and characterized the splicing machinery from the red alga Cyanidioschyzon merolae, which has been reported to harbor only 26 intron-containing genes. The U2, U4, U5, and U6 snRNAs contain expected conserved sequences and have the ability to adopt secondary structures and form intermolecular base-pairing interactions, as in other organisms. C. merolae has a highly reduced set of 43 identifiable core splicing proteins, compared with ∼90 in budding yeast and ∼140 in humans. Strikingly, we have been unable to find a U1 snRNA candidate or any predicted U1-associated proteins, suggesting that splicing in C. merolae may occur without the U1 small nuclear ribonucleoprotein particle. In addition, based on mapping the identified proteins onto the known splicing cycle, we propose that there is far less compositional variability during splicing in C. merolae than in other organisms. The observed reduction in splicing factors is consistent with the elimination of spliceosomal components that play a peripheral or modulatory role in splicing, presumably retaining those with a more central role in organization and catalysis.pre-mRNA splicing | spliceosome core | U1 snRNP | genome reduction | splicing mechanism P re-mRNA splicing occurs by two transesterification reactions that are catalyzed by the spliceosome, a large macromolecular assembly of five snRNAs and more than 200 proteins in humans (1). These components are thought to assemble onto each new pre-mRNA transcript in an ordered fashion through the recognition and binding of three highly conserved sequences in the transcript: the 5′ splice site, the branch site, and the 3′ splice site (2, 3). Some of these interactions occur via direct RNA/RNA base pairing between the transcript and snRNAs; for example, both U1 and U6 snRNAs base pair to the 5′ splice site of the pre-mRNA transcript, and, similarly, U2 snRNA base pairs to the branch site (3).Given the complexity of the human spliceosome, it is of considerable interest to find a more tractable splicing system with fewer components to study the core processes of splicing (assembly, catalysis, and fidelity). The Saccharomyces cerevisiae (yeast) spliceosome has been proposed as a simplified model system, because it contains only about 100 proteins (4). Indeed, substantial progress in understanding the spliceosome has been made by studying yeast splicing (3,5). Nevertheless, the yeast spliceosome is still a highly complex system in which to investigate the role of individual proteins, let alone attempt ...

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“…Prp19 (precursor RNA processing 19) is an essential member of the Prp19 complex (PrpC, also known as NTC, or 19 Complex) which plays important roles in mRNA maturation (transcription elongation, splicing and export), genome stability, and protein degradation (Chanarat and SträSSer, 2013). Besides its nuclear localization, it was identified as a component of lipid droplets (Cho et al, 2007).…”

Section: Associations With the Nucleusmentioning

confidence: 99%

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

2017

Frontiers Research Topics

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Splicing and beyond: The many faces of the Prp19 complex

Cited by 128 publications

References 92 publications

Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5

Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5

Dramatically reduced spliceosome in Cyanidioschyzon merolae

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

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