SLU7: A New Hub of Gene Expression Regulation-From Epigenetics to Protein Stability in Health and Disease

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Nov 11

PMID 36362191

Authors

Maria Garate-Rascon

Miriam Recalde

Carla Rojo

Maite G Fernandez-Barrena

Matias A Avila

Maria Arechederra

Carmen Berasain

Affiliations

Soon will be listed here.

Abstract

SLU7 (Splicing factor synergistic lethal with U5 snRNA 7) was first identified as a splicing factor necessary for the correct selection of 3' splice sites, strongly impacting on the diversity of gene transcripts in a cell. More recent studies have uncovered new and non-redundant roles of SLU7 as an integrative hub of different levels of gene expression regulation, including epigenetic DNA remodeling, modulation of transcription and protein stability. Here we review those findings, the multiple factors and mechanisms implicated as well as the cellular functions affected. For instance, SLU7 is essential to secure liver differentiation, genome integrity acting at different levels and a correct cell cycle progression. Accordingly, the aberrant expression of SLU7 could be associated with human diseases including cancer, although strikingly, it is an essential survival factor for cancer cells. Finally, we discuss the implications of SLU7 in pathophysiology, with particular emphasis on the progression of liver disease and its possible role as a therapeutic target in human cancer.

Citing Articles

Caspases compromise SLU7 and UPF1 stability and NMD activity during hepatocarcinogenesis.

Rojo C, Garate-Rascon M, Recalde M, Alava A, Elizalde M, Azkona M JHEP Rep. 2024; 6(8):101118.

PMID: 39105183 PMC: 11298840. DOI: 10.1016/j.jhepr.2024.101118.

Cryptococcus neoformans Slu7 ensures nuclear positioning during mitotic progression through RNA splicing.

Krishnan V, Negi M, Peesapati R, Vijayraghavan U PLoS Genet. 2024; 20(5):e1011272.

PMID: 38768219 PMC: 11142667. DOI: 10.1371/journal.pgen.1011272.

G3BP1 and SLU7 Jointly Promote Immune Evasion by Downregulating MHC-I via PI3K/Akt Activation in Bladder Cancer.

Zheng X, Chen J, Deng M, Ning K, Peng Y, Liu Z Adv Sci (Weinh). 2023; 11(7):e2305922.

PMID: 38084438 PMC: 10870071. DOI: 10.1002/advs.202305922.

References

Tschan M, Simon H . The role of autophagy in anticancer therapy: promises and uncertainties. J Intern Med. 2010; 268(5):410-8. DOI: 10.1111/j.1365-2796.2010.02266.x. View

Mendell J . miRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008; 133(2):217-22. PMC: 2732113. DOI: 10.1016/j.cell.2008.04.001. View

Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez F, Talianidis I . Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006; 20(16):2293-305. PMC: 1553211. DOI: 10.1101/gad.390906. View

Tannapfel A, John K, Mise N, Schmidt A, Buhlmann S, Ibrahim S . Autonomous growth and hepatocarcinogenesis in transgenic mice expressing the p53 family inhibitor DNp73. Carcinogenesis. 2007; 29(1):211-8. DOI: 10.1093/carcin/bgm236. View

Topper M, Vaz M, Marrone K, Brahmer J, Baylin S . The emerging role of epigenetic therapeutics in immuno-oncology. Nat Rev Clin Oncol. 2019; 17(2):75-90. PMC: 7254932. DOI: 10.1038/s41571-019-0266-5. View

Onn I, Heidinger-Pauli J, Guacci V, Unal E, Koshland D . Sister chromatid cohesion: a simple concept with a complex reality. Annu Rev Cell Dev Biol. 2008; 24:105-29. DOI: 10.1146/annurev.cellbio.24.110707.175350. View

Khamzina L, Gruppuso P, Wands J . Insulin signaling through insulin receptor substrate 1 and 2 in normal liver development. Gastroenterology. 2003; 125(2):572-85. DOI: 10.1016/s0016-5085(03)00893-x. View

Ubhi T, Brown G . Exploiting DNA Replication Stress for Cancer Treatment. Cancer Res. 2019; 79(8):1730-1739. DOI: 10.1158/0008-5472.CAN-18-3631. View

Jeong S . SR Proteins: Binders, Regulators, and Connectors of RNA. Mol Cells. 2017; 40(1):1-9. PMC: 5303883. DOI: 10.14348/molcells.2017.2319. View

10.

Kornblihtt A, Schor I, Allo M, Dujardin G, Petrillo E, Munoz M . Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol. 2013; 14(3):153-65. DOI: 10.1038/nrm3525. View

11.

Karamysheva Z, Diaz-Martinez L, Warrington R, Yu H . Graded requirement for the spliceosome in cell cycle progression. Cell Cycle. 2015; 14(12):1873-83. PMC: 4614359. DOI: 10.1080/15384101.2015.1039209. View

12.

Frank D, Patterson B, Guthrie C . Synthetic lethal mutations suggest interactions between U5 small nuclear RNA and four proteins required for the second step of splicing. Mol Cell Biol. 1992; 12(11):5197-205. PMC: 360453. DOI: 10.1128/mcb.12.11.5197-5205.1992. View

13.

Hervouet E, Nadaradjane A, Gueguen M, Vallette F, Cartron P . Kinetics of DNA methylation inheritance by the Dnmt1-including complexes during the cell cycle. Cell Div. 2012; 7:5. PMC: 3307489. DOI: 10.1186/1747-1028-7-5. View

14.

Rankin S, Ayad N, Kirschner M . Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates. Mol Cell. 2005; 18(2):185-200. DOI: 10.1016/j.molcel.2005.03.017. View

15.

Fagerberg L, Hallstrom B, Oksvold P, Kampf C, Djureinovic D, Odeberg J . Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2013; 13(2):397-406. PMC: 3916642. DOI: 10.1074/mcp.M113.035600. View

16.

Baylin S, Esteller M, Rountree M, Bachman K, Schuebel K, Herman J . Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet. 2001; 10(7):687-92. DOI: 10.1093/hmg/10.7.687. View

17.

Baralle F, Giudice J . Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 2017; 18(7):437-451. PMC: 6839889. DOI: 10.1038/nrm.2017.27. View

18.

Frank D, Guthrie C . An essential splicing factor, SLU7, mediates 3' splice site choice in yeast. Genes Dev. 1992; 6(11):2112-24. DOI: 10.1101/gad.6.11.2112. View

19.

Petasny M, Bentata M, Pawellek A, Baker M, Kay G, Salton M . Splicing to Keep Cycling: The Importance of Pre-mRNA Splicing during the Cell Cycle. Trends Genet. 2020; 37(3):266-278. DOI: 10.1016/j.tig.2020.08.013. View

20.

Bolotin E, Liao H, Ta T, Yang C, Hwang-Verslues W, Evans J . Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays. Hepatology. 2010; 51(2):642-53. PMC: 3581146. DOI: 10.1002/hep.23357. View