A methyl transferase links the circadian clock to the regulation of alternative splicing

Sanchez, Sabrina E.; Petrillo, Ezequiel; Beckwith, Esteban J.; Zhang, Xu; Rugnone, Mathias L.; Hernando, Carlos Esteban; Cuevas, Juan C.; Herz, Micaela Amalia Godoy; Depetris-Chauvin, Ana; Simpson, Craig G.; Brown, John W.; Cerdán, Pablo D.; Borevitz, Justin O.; Más, Paloma Díaz; Ceriani, M. Fernanda; Kornblihtt, Alberto R.; Yanovsky, Marcelo J.

doi:10.1038/nature09470

Cited by 267 publications

(336 citation statements)

References 45 publications

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“…By global analysis using tiling arrays as well as a high-resolution RT-PCR panel, it has been shown that the lack of PRMT5 modifies alternative splicing patterns in both Arabidopsis thaliana and Drosophila melanogaster. Alternative splicing changes were detected among others, in clock core and clock-related genes, affecting the circadian rhythm of the mutant organisms (46).…”

Section: Post-translational Modifications Of Sr Proteins: Above and Bmentioning

confidence: 99%

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

et al. 2012

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SummarySerine/arginine-rich (SR) proteins are among the most studied splicing regulators. They constitute a family of evolutionarily conserved proteins that, apart from their initially identified and deeply studied role in splicing regulation, have been implicated in genome stability, chromatin binding, transcription elongation, mRNA stability, mRNA export and mRNA translation. Remarkably, this list of SR protein activities seems far from complete, as unexpected functions keep being unraveled. An intriguing aspect that awaits further investigation is how the multiple tasks of SR proteins are concertedly regulated within mammalian cells. In this article, we first discuss recent findings regarding the regulation of SR protein expression, activity and accessibility. We dive into recent studies describing SR protein auto-regulatory feedback loops involving different molecular mechanisms such as unproductive splicing, microRNA-mediated regulation and translational repression. In addition, we take into account another step of regulation of SR proteins, presenting new findings about a variety of post-translational modifications by proteomics approaches and how some of these modifications can regulate SR protein sub-cellular localization or stability. Towards the end, we focus in two recently revealed functions of SR proteins beyond mRNA biogenesis and metabolism, the regulation of micro-RNA processing and the regulation of small ubiquitin-like modifier (SUMO) conjugation.

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Section: Post-translational Modifications Of Sr Proteins: Above and Bmentioning

confidence: 99%

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

et al. 2012

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“…Not only CCA1, but other circadian clock-related genes, including LHY, TOC1, PRR3, PRR5, PRR7, PRR9, ZTL and GI, undergo alternative splicing in Arabidopsis, mostly in a temperature-dependent manner. 80,88,89 The role of PROTEIN ARGININE METHYL TRANSFERASE 5 (AtPRMT5) in regulating the alternative splicing of PRR9 was discovered recently. 89 AtPRMT5 is a type II protein arginine methyltransferase that methylates diverse substrates and affects pre-mRNA splicing in a global fashion.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…80,88,89 The role of PROTEIN ARGININE METHYL TRANSFERASE 5 (AtPRMT5) in regulating the alternative splicing of PRR9 was discovered recently. 89 AtPRMT5 is a type II protein arginine methyltransferase that methylates diverse substrates and affects pre-mRNA splicing in a global fashion. AtPRMT5 methylates various nonhistone substrates, including RNA processing factors, hnRNPs, U snRNP, AtSmD1, D3 and AtLSm4.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…91 Mutations in Atprmt5 reduce the methylation of AtSmD1 and AtLSm4, leading to splicing defects in hundreds of genes that are involved in multiple processes, probably by regulating 5' splice site recognition. 89,90 Defects in the alternative splicing of PRR9 in atprmt5-5 lengthen the circadian period, indicating the regulatory role of alternative splicing in the clock. 89 The involvement of splicing factors such as Ski-interacting protein (SKIP) and SPLICEOSOMAL TIMEKEEPER LOCUS1 (STIPL1) in the regulation of the circadian clock in Arabidopsis has also been demonstrated recently.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…89,90 Defects in the alternative splicing of PRR9 in atprmt5-5 lengthen the circadian period, indicating the regulatory role of alternative splicing in the clock. 89 The involvement of splicing factors such as Ski-interacting protein (SKIP) and SPLICEOSOMAL TIMEKEEPER LOCUS1 (STIPL1) in the regulation of the circadian clock in Arabidopsis has also been demonstrated recently. 92,93 Mutations in AtSKIP and STIPL1 increase the period length of the circadian clock.…”

Section: Acknowledgmentsmentioning

confidence: 99%

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