Functional Interaction between U1snRNP and Sam68 Insures Proper 3′ End Pre-mRNA Processing during Germ Cell Differentiation

Naro, Chiara; Pellegrini, Livia; Jolly, Ariane; Farini, Donatella; Cesari, E.; Bielli, Pamela; Grange, Pierre de la; Sette, Claudio

doi:10.1016/j.celrep.2019.02.058

Cited by 37 publications

(47 citation statements)

References 46 publications

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“…This study focused on the neuronal isoform selection in 3′ UTR by SAM68 and demonstrated their functional aspects through the identification of a novel target IL1RAP in neurons (Figure 5). Very recently, two articles also elucidated the interaction between SAM68 and U1 small nuclear ribonucleoprotein particle (snRNP) as a global mechanism underlying ALE regulation by SAM68 (Naro et al., 2019, Subramania et al., 2019), supporting our findings in the CNS. U1 snRNP prevents premature transcript termination by inhibition of cryptic PASs (Berg et al., 2012, Kaida et al., 2010).…”

Section: Discussionsupporting

confidence: 85%

SAM68-Specific Splicing Is Required for Proper Selection of Alternative 3′ UTR Isoforms in the Nervous System

et al. 2019

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Neuronal alternative splicing is a core mechanism for functional diversification. We previously found that STAR family proteins (SAM68, SLM1, SLM2) regulate spatiotemporal alternative splicing in the nervous system. However, the whole aspect of alternative splicing programs by STARs remains unclear. Here, we performed a transcriptomic analysis using SAM68 knockout and SAM68/SLM1 double-knockout midbrains. We revealed different alternative splicing activity between SAM68 and SLM1; SAM68 preferentially targets alternative 3 0 UTR exons. SAM68 knockout causes a long-to-short isoform switch of a number of neuronal targets through the alteration in alternative last exon (ALE) selection or alternative polyadenylation. The altered ALE usage of a novel target, interleukin 1 receptor accessory protein (Il1rap), results in remarkable conversion from a membrane-bound type to a secreted type in Sam68 KO brains. Proper ALE selection is necessary for IL1RAP neuronal function. Thus the SAM68-specific splicing program provides a mechanism for neuronal selection of alternative 3 0 UTR isoforms.

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Section: Discussionsupporting

confidence: 85%

SAM68-Specific Splicing Is Required for Proper Selection of Alternative 3′ UTR Isoforms in the Nervous System

et al. 2019

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“…Sam68 promotes exon 2 inclusion ( Fig. 2d, e) and it cooperates with the spliceosomal U1snRNP in exon recognition 28,22 . Analysis of testes from juvenile Sam68 knockout mice (P10) showed a significant reduction in Spo11 exon 2 inclusion (Fig.…”

Section: A Reduced Rnapii Elongation Rate Promotes Splicing Of Spo11αmentioning

confidence: 93%

Combinatorial control of Spo11 alternative splicing by modulation of RNA polymerase II dynamics and splicing factor recruitment during meiosis

et al. 2020

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Homologous recombination and chromosome segregation in meiosis rely on the timely expression of two splice variants of the endonuclease SPO11, named α and β, which respectively skip or include exon 2. However, in spite of its physiological importance, the mechanism underlying Spo11 alternative splicing in meiosis is still unknown. By screening the activity of factors that are predicted to bind the alternatively spliced region of Spo11, we identified hnRNPH as a key regulator of SPO11α splicing in mouse spermatocytes. Although hnRNPH was not upregulated in meiosis concomitantly with the switch in splicing, its recruitment to Spo11 pre-mRNA was favored by selective modulation of RNA polymerase II (RNAPII) phosphorylation and processivity in proximity of exon 2. The hnRNPH binding sites were localized near those of splicing factors that promote SPO11β splicing, suggesting that hnRNPH favors exon 2 skipping by competing out positive regulators. Indeed, hnRNPH binds proximal to a consensus motif for Sam68, a positive regulator of SPO11β splicing in vitro and in vivo, and it interferes with Sam68 binding to the Spo11 pre-mRNA. Thus, our work reveals that modulation of RNAPII dynamics in concert with hnRNPH recruitment exerts a combinatorial control of the timely regulated Spo11 splicing during meiosis.

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“…Notably, ZFC3H1, which is specific to PAXT (Meola et al, 2016), was as abundant as the NEXT adaptor ZCCHC8 in Biotin-U1 AMO XLPD-MS (Table S4). Sam68/KHDRBS1 has been recently shown to bind in proximity to U1 and play a role in 3 0 end processing in germ cells (Naro et al, 2019). Thus, U1-CPAFs at the first 5 0 ss plays a crucial role in telescripting in genes with long first introns.…”

Section: U1 Amo Activates U1-cpafs Without Releasing U1mentioning

confidence: 99%

A Complex of U1 snRNP with Cleavage and Polyadenylation Factors Controls Telescripting, Regulating mRNA Transcription in Human Cells

Cai

et al. 2019

Molecular Cell

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Functional Interaction between U1snRNP and Sam68 Insures Proper 3′ End Pre-mRNA Processing during Germ Cell Differentiation

Cited by 37 publications

References 46 publications

SAM68-Specific Splicing Is Required for Proper Selection of Alternative 3′ UTR Isoforms in the Nervous System

SAM68-Specific Splicing Is Required for Proper Selection of Alternative 3′ UTR Isoforms in the Nervous System

Combinatorial control of Spo11 alternative splicing by modulation of RNA polymerase II dynamics and splicing factor recruitment during meiosis

A Complex of U1 snRNP with Cleavage and Polyadenylation Factors Controls Telescripting, Regulating mRNA Transcription in Human Cells

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