SON is a spliceosome-associated factor required for mitotic progression

Huen, Michael S.Y.; Sy, Shirley M.-H.; Leung, Ka Man; Ching, Yick–Pang; Tipoe, George L.; Man, Cornelia; Dong, Shuang; Chen, Junjie

doi:10.4161/cc.9.13.12151

Cited by 36 publications

(61 citation statements)

References 27 publications

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“…18,108 Depletion of SON in cancerous cells resulted in mitotic arrest, with severe impairment of spindle pole segregation and genome integrity, due to aberrant splicing of pre-mRNAs whose protein products are involved in cell cycle progression and mitosis. [108][109][110] Prolonged depletion of MALAT1 in human cancerous cells also revealed mitotic arrest with abnormal microtubule organization and chromosome segregation defects. 18 MALAT1-depleted cells also showed abnormal nuclear structures, including micronuclei and nuclear lobes similar to the phenotypes observed upon SON depletion.…”

Section: Transcriptional Regulationmentioning

confidence: 97%

“…18 Of particular interest is SON, an SR-related speckle-associated protein, which is suggested to act as the scaffold for the proper organization of speckle components and also to function as a coactivator for efficient RNA processing. [108][109][110] Depletion of SON resulted in the redistribution of MALAT1 from nuclear speckles to a more homogenous nuclear distribution. 18 On the other hand, SON continued to localize to speckles in MALAT1-depleted cells, indicating that only SON influences the MALAT1 association to speckles and not vice versa.…”

Section: Transcriptional Regulationmentioning

confidence: 98%

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RNA splicing control

2011

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The mammalian genome harbors a large number of long non-coding RNAs (lncRNAs) that do not code for proteins, but rather they exert their function directly as RNA molecules. LncRNAs are involved in executing several vital cellular functions. They facilitate the recruitment of proteins to specific chromatin sites, ultimately regulating processes like dosage compensation and genome imprinting. LncRNAs are also known to regulate nucleocytoplasmic transport of macromolecules. A large number of the regulatory lncRNAs are retained within the cell nucleus and constitute a subclass termed nuclear-retained RNAs (nrRNAs). NrRNAs are speculated to be involved in crucial gene regulatory networks, acting as structural scaffolds of subnuclear domains. NrRNAs modulate gene expression by influencing chromatin modification, transcription and post-transcriptional gene processing. The cancer-associated Metastasis-associated lung adenocarcinoma transcript1 (MALAT1) is one such long nrRNA that regulates pre-mRNA processing in mammalian cells. Thus far, our understanding about the roles played by nrRNAs and their relevance in disease pathways is only 'a tip of an iceberg'. It will therefore be crucial to unravel the functions for the vast number of long nrRNAs, buried within the complex mine of the human genome.

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Section: Transcriptional Regulationmentioning

confidence: 97%

Section: Transcriptional Regulationmentioning

confidence: 98%

RNA splicing control

2011

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“…These results are in agreement with and extend previously reported roles for other spliceosome components in mitosis. 11,12,31 Different degrees of SNRPB depletion produce distinct cell cycle phenotypes…”

Section: Spliceosome Depletion Increases Dna Damage and Elicits A G2 mentioning

confidence: 99%

“…17,18 A connection between the spliceosome and cell cycle progression has been found in many organisms including budding yeast, [19][20][21][22][23][24] fission yeast, [25][26][27] Drosophila, 9,28 chicken, 29 mouse, 30 and human cells. 6,11,12,29,31,32 In human cells, depletion of different spliceosome components with siRNAs results in multiple cell cycle defects, with most siRNAs analyzed eliciting mitotic defects 6,11,12,31 although accumulation of cells in S phase 32 has also been observed. The mitotic defects observed after spliceosome depletion have been linked to splicing defects affecting the chromosome cohesion protein sororin 11,12 and Apc2, 11 a subunit of the anaphase-promoting complex/cyclosome (APC/C) required for mitotic progression.…”

Section: Introductionmentioning

confidence: 99%

Graded requirement for the spliceosome in cell cycle progression

Karamysheva¹,

Díaz-Martínez

Warrington

et al. 2015

Cell Cycle

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Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions.

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“…One of the top ten candidates is the spliceosome-associated factor SON, which was initially proposed to be a potential DNA-binding protein 15,16 . Recent studies suggest that SON is a protein localized in nuclear speckles 17,18 , and that it is involved in cell-cycle progression and pre-messenger RNA processing 19–22 . Furthermore, SON was shown to physically interact with the spliceosome and deficiency of SON compromises spliceosome function in HeLa cells 19,21 .…”

mentioning

confidence: 99%

SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells

et al. 2013

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Human embryonic stem cells (hESCs) harbour the ability to undergo lineage-specific differentiation into clinically relevant cell types. Transcription factors and epigenetic modifiers are known to play important roles in the maintenance of pluripotency of hESCs. However, little is known about regulation of pluripotency through splicing. In this study, we identify the spliceosome-associated factor SON as a factor essential for the maintenance of hESCs. Depletion of SON in hESCs results in the loss of pluripotency and cell death. Using genome-wide RNA profiling, we identified transcripts that are regulated by SON. Importantly, we confirmed that SON regulates the proper splicing of transcripts encoding for pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24. Furthermore, we show that SON is bound to these transcripts in vivo. In summary, we connect a splicing-regulatory network for accurate transcript production to the maintenance of pluripotency and self-renewal of hESCs.

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SON is a spliceosome-associated factor required for mitotic progression

Cited by 36 publications

References 27 publications

RNA splicing control

RNA splicing control

Graded requirement for the spliceosome in cell cycle progression

SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells

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