The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex

Zhang, Lin; Wan, Yufeng; Huang, Guobin; Wang, Dongni; Yu, Xinyang; Huang, Guo N.; Guo, Jinhu

doi:10.1038/srep13403

Cited by 19 publications

(20 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent data suggest that the exosome may play a role in normal turnover of spliceosomal RNAs, as knockdown of the exosome exonuclease Rrp44 resulted in higher levels of U6 (Zhang et al 2015). The presence of a terminal phosphate (in yeast) or 2 ′ ,3 ′ -cyclic phosphate (in humans) on U6 may inhibit degradation by the exosome, as the nuclear exosome-associated exonuclease Rrp6 is inactive on a 3 ′ phosphate-terminated RNA (Burkard and Butler 2000).…”

Section: Degradationmentioning

confidence: 99%

The life of U6 small nuclear RNA, from cradle to grave

Didychuk

Butcher

Brow

2018

RNA

View full text Add to dashboard Cite

Removal of introns from precursor messenger RNA (pre-mRNA) and some noncoding transcripts is an essential step in eukaryotic gene expression. In the nucleus, this process of RNA splicing is carried out by the spliceosome, a multi-megaDalton macromolecular machine whose core components are conserved from yeast to humans. In addition to many proteins, the spliceosome contains five uridine-rich small nuclear RNAs (snRNAs) that undergo an elaborate series of conformational changes to correctly recognize the splice sites and catalyze intron removal. Decades of biochemical and genetic data, along with recent cryo-EM structures, unequivocally demonstrate that U6 snRNA forms much of the catalytic core of the spliceosome and is highly dynamic, interacting with three snRNAs, the pre-mRNA substrate, and >25 protein partners throughout the splicing cycle. This review summarizes the current state of knowledge on how U6 snRNA is synthesized, modified, incorporated into snRNPs and spliceosomes, recycled, and degraded.

show abstract

Section: Degradationmentioning

confidence: 99%

The life of U6 small nuclear RNA, from cradle to grave

Didychuk

Butcher

Brow

2018

RNA

View full text Add to dashboard Cite

show abstract

“…Misregulation of RNA processing frequently leads to an altered circadian FRP (Jones et al, 2012;Wang et al, 2012;MacGregor et al, 2013;Perez-Santángelo et al, 2014) and alternate splicing contributes to modifications to the circadian system in response to temperature and drought (James et al, 2012;Filichkin et al, 2015). Similarly, circadian regulation of exosome activity has previously been implicated in the circadian system of the bread mold Neurospora crassa (Guo et al, 2009;Zhang et al, 2015).…”

Section: Loss Of Xrn Activity Replicates the Circadian Phenotypes Of mentioning

confidence: 99%

3′-Phosphoadenosine 5′-Phosphate Accumulation Delays the Circadian System

2018

View full text Add to dashboard Cite

The circadian system optimizes cellular responses to stress, but the signaling pathways that convey the metabolic consequences of stress into this molecular timekeeping mechanism remain unclear. Redox regulation of the SAL1 phosphatase during abiotic stress initiates a signaling pathway from chloroplast to nucleus by regulating the accumulation of a metabolite, 3'-phosphoadenosine 5'-phosphate (PAP). Consequently, PAP accumulates in response to redox stress and inhibits the activity of exoribonucleases (XRNs) in the nucleus and cytosol. We demonstrated that osmotic stress induces a lengthening of circadian period and that genetically inducing the SAL1-PAP-XRN pathway in plants lacking either SAL1 or XRNs similarly delays the circadian system. Exogenous application of PAP was also sufficient to extend circadian period. Thus, SAL1-PAP-XRN signaling likely regulates circadian rhythms in response to redox stress. Our findings exemplify how two central processes in plants, molecular timekeeping and responses to abiotic stress, can be interlinked to regulate gene expression.

show abstract

“…MTR4 is present in the TRMAP complex, the nuclear exosome targeting (NEXT) complex and poly-A tail exosome targeting (PAXT) complex for RNA decay, suggesting that MTR4 targets a broad spectrum of RNA and regulates their stability. MTR4 has not been shown to play important roles in alternative splicing (AS), but the exosome is involved in chromatin remodeling and normal processing of various RNAs such as pre-mRNA splicing [6][7][8][9] . While the biochemical functions of MTR4 have been extensively investigated, the physiological roles of MTR4 in development and disease remain unclear.…”

mentioning

confidence: 99%

MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing

Kim

Jiang

et al. 2020

Nat Commun

View full text Add to dashboard Cite

The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC.

show abstract

The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex

Cited by 19 publications

References 60 publications

The life of U6 small nuclear RNA, from cradle to grave

The life of U6 small nuclear RNA, from cradle to grave

3′-Phosphoadenosine 5′-Phosphate Accumulation Delays the Circadian System

MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing

Contact Info

Product

Resources

About