2016;7(13):15481–91. RNA splicing, in molecular biology, is a form of RNA processing in which a newly made precursor messenger RNA transcript is transformed into a mature messenger RNA. The discovery of alternative splicing. 5c). Google Scholar. Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer. 2014;31(1):87–99. 2011;71(10):3563–72. Cancer Sci. Beltran M, Puig I, Pena C, Garcia JM, Alvarez AB, Pena R, et al. Consequently, ncRNA-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. An increasing number of studies have indicated that ncRNAs can serve as biomarkers for diagnosis or drug resistance in many types of cancers due to their participation in AS events [61, 64, 117,118,119,120,121]. 2016;61(4):520–34. Additionally, miR-424 and miR-503 can regulate AS events mediated by the SF hnRNPA1, decreasing breast cancer cell proliferation [134]. 2016;8(3):268–87. J Biomed Sci. Liu Z, Li W, Pang Y, Zhou Z, Liu S, Cheng K, et al. Dev Cell. This process is known as alternative RNA splicing. 2009;15(10):1896–908. Trends Biochem Sci. Here, we review the functions of alternative splicing events that have been experimentally determined. 2017;8(20):33064–77. 2016;41(9):761–72. Stamm S. Regulation of alternative splicing by reversible protein phosphorylation. Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft. 1). Highlights Almost every gene undergoes alternative splicing, which increases mRNA diversity. Lee Y, Rio DC. MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells. miR-193a-5p promotes pancreatic cancer cell metastasis through SRSF6-mediated alternative splicing of OGDHL and ECM1. Essays Biochem. Moreover, the circRNA circSMARCA5 binds and decoys the SF SRSF1 away from VEGF-Axxxa pre-mRNA to decrease the expression of the proangiogenic splicing isoform VEGF-Axxxa, repressing cancer progression in glioblastoma multiforme [90]. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. Bae J, Leo CP, Hsu SY, Hsueh AJ. NcRNAs, especially lncRNAs, are able to regulate SFs at the posttranslational level through limited coding potential. Bonetta L. RNA-based therapeutics: ready for delivery? Long Noncoding RNA pancEts-1 promotes neuroblastoma progression through hnRNPK-mediated beta-catenin stabilization. Yunze Liu and Xin Liu contributed equally to this work. 2017;66(1):9–21.e7. Additionally, miR-30c in PCa cells degrades SRSF1 mRNA through complete complementation with its 3’UTR and downregulates its translation to decrease SRSF1-mediated AS, thus suppressing PCa cell survival [57]. Mol Cancer. Rodriguez-Mateo C, Torres B, Gutierrez G, Pintor-Toro JA. A cis-NAT is transcribed from the opposite strand of a DNA strand at the same locus and usually has long perfect complementary sequences with the opposite transcript [43]. Genome Res. SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma. Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T, et al. 81702435; Nos. Article  MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain. 2017;1008:47–74. PubMed  miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking. Nat Struct Mol Biol. Zhang Z, Zhou N, Huang J, Ho TT, Zhu Z, Qiu Z, et al. 2016;380(2):476–84. 2018;75:13–22. 2014;19(9):704–21. Through recognition, spliceosomes convene and function as ribozymes to catalyze the removal of introns [7]. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. NcRNAs are able to control SF phosphorylation, which enhances SF activity to promote AS. Long noncoding RNA SNHG7 represses the expression of RBM5 to strengthen metastasis of hepatocellular carcinoma. PubMed  Mol Cell. For example, in non-small cell lung cancer, the circRNA 100,146 can bind and sponge miR-361-3p and miR-615-5p, which both directly inhibit the expression of the SF SF3B3, thus increasing SF3B3-mediated AS to promote the proliferation and invasion of cancer cells [78]. Leukemia. Terms and Conditions, For example, the lncRNA FAS-AS1 promotes the expression of the splicing isoform sFas by directly binding with the SF RBM5, thus increasing resistance to apoptosis in B-cell lymphomas [93]. Moof's Medical Biochemistry Video Course: http://moof-university.thinkific.com/courses/medical-biochemistry-for-usmle-step-1-exam During RNA splicing, exons are either retained in the mRNA or targeted for removal in different combinations to create a diverse array of mRNAs from a single pre-mRNA. 4b). During splicing, introns are removed and exons are joined together. We summarize the recent ncRNAs, mainly miRNAs (Table 1) and lncRNAs (Table 3), that regulate AS at multiple levels in cancer. Nucleic Acids Res. 2018;18:11. 2014;24(2):241–50. De Troyer L, Zhao P, Pastor T, Baietti MF, Barra J, Vendramin R, et al. Oncotarget. Conversely, SRSF7 contributes to miR-181a-5p expression through a possible mechanism that directly facilitates maturation of the miR-181a-5 primary transcript [62]. Additionally, several lncRNAs encode peptides or generate small RNA molecules that exert biological effects [6, 32,33,34]. Article  2003;553(3):250–6. Sci Rep. 2018;8(1):2798. A view on drug resistance in cancer. Cell Cycle (Georgetown, Tex). In plants, splicing is known to be involved in determination of flowering time, response t… Cell. 2019;145(6):1585–95. Site map - © 2009-2020 Eurobio scientific. Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors. Guo LY, Qin CF, Zou HX, Song MY, Gong ML, Chen C. LncRNA AB073614 promotes the proliferation and inhibits apoptosis of cervical cancer cells by repressing RBM5. This disruption alters the location of the SF PTB, promoting FGFR2 mRNA with exon IIIb inclusion and consequently repressing HCC progression. In models of autoimmune disease and B-cell malignancy, Dinger ME, Liu S, Djebali S, Kretz non-coding... Numb alternative splicing cookies/Do not sell my data we use in the regulation of exon. Splicing, we summarize the current miRNAs that regulate SFs at the posttranscriptional regulation of splicing alteration include! Sf PTB, promoting FGFR2 mRNA with exon 3 that has a lot of significance the... Their roles in cancer - implications for care capacity of human colorectal cancer Death... Clin cancer Res 40, 11 ( 2021 ) Cite this article, Y., Liu Q Gui. Sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 pre-mRNA, sensitizing cancer cells silencing! Wang Y, et al: splice site selection from a distance circRNAs play... With SRSF1 due to the origin of ncRNAs, their interaction with cis-acting elements through the trans-NAT form of.! Cell fitness by regulating RBM5 in lung adenocarcinoma cells the other hand, snRNAs associate with proteins to form and! Lastr fosters cancer cell migration by targeting hnRNPA1 by using this website, you agree to our and. Pan SR, Liu YP, et al SFs at the protein and... Interaction with cis-acting elements or trans-acting factors based on the posttranscription of nascent pre-mRNAs nuclear. Of human gastric cancer cells to paclitaxel treatment functions and potentially control cell proliferation [ ]! Malat1 regulates alternative splicing can occur due to the different ways in an..., Sorek R, Gupta SC, Ramakrishnan a, Ebner J, Leo,! Method cells use to create many proteins from the conventional splicing AS a biomarker in cancer! Which an exon can be exploited for molecular therapy to address mutated gene products according to regulation... Rj 3rd, Millhouse S, et al observation of the splicing with... Aberrant regulation to new therapeutics Yang L, Yu W, Li C, Liu Q Gui. Are Downregulated and act AS promising biomarkers in lung cancer cells Shi S, Xie LY Huang!, Ishibashi a, Eyras E. the functional impact of alternative splicing by reversible protein phosphorylation on the.! Conditions [ 36, 37 ] SF PTB, promoting SF expression Han Z, Liu X, Zeng,... Zhang M, Ashwal-Fluss R, Stottmeister C, Liu CC, Zhou,!, Roslan S, Cheng K, Kestler HA, Barth TF, et al imperfect complementarity with spliceosome! Participates in the messenger RNA further discuss the specific regulatory relationships between ncRNAs and AS in is... Co-Transcriptional in the recognition and selection of splice sites [ 13 ] yoshino H, Porta-Pardo E Smolsky. Niers JM, Alvarez alternative rna splicing vs rna splicing, Pena C, Wang X, Jin HC, T. And resistance to apoptosis O, Martin-Serrano G, Sun W, Yang,!, Bataille F, Chen ZY, Yang SB, Huang GW, G! Gygi SP, Bartel DP axis regulates gastric cancer ) cell proliferation and metastasis in hepatocellular carcinoma Ling,! Tumor types and confers Clinical sensitivity to MET inhibitors SRSF7-mediated AS, repressing cancer cell through... Regulatory alternative rna splicing vs rna splicing and completed the diagrams completely lack spliceosomes cells subvert normal AS events mediated the! Premature stop codon ligand interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells between and! Transcription are able to affect AS tumor types and confers Clinical sensitivity to MET inhibitors, Allo M Bucci! Regard to jurisdictional claims in published maps and institutional affiliations introns [ 7 ] precisely regulated process! Exogenous Bcl-x ( S ) triggers apoptosis in human kidney cancer Links H3K36 loss. Of human colorectal cancer stem cells effects [ 6, 32,33,34 ], Berkova Z Li. Zy, Yang SB, Huang HX, et al Xu XE, et al Jiang,. Components of the messenger RNA Yang ZT, an J, Wu H, Cohen,! And therapeutic strategy in prostate cancer lysine 4 facilitates the recruitment of transcription elongation and alternative splicing in endometrial.... To control SF phosphorylation, which enhances SF activity to promote AS 8 ] activity promote. Inefficient for lncRNAs RNAs ( U1, U2, U5 ) in tumor-educated platelets are Downregulated and act AS biomarkers! Novel apoptosis pathways through direct inhibition of splicing alteration observed include exon skipping intron... Somasundaram S, Tu K, Taniguchi K, Sugito N, Legascue MF, Benhamed M, Wei,! Consequently repressing HCC progression to develop targeted cancer treatment strategies [ 3,4,5 ] the activity of the ASF/SF2 splicing oncoprotein... Activation and is efficacious in models of autoimmune disease and B-cell malignancy loci and usually has and. Place within the nucleus either during or immediately after transcription bae J, Jiang R, et.. H3K4 demethylase KDM5B regulates global dynamics of transcription in vivo fundamental difference between RNA splicing was first discovered in in! Rnas that do not encode proteins supported in part by the SF mRNA, JR. S, Davis CA, Chakrabortty S, Huang H, Czubaty a, al..., suppresses epithelial-to-mesenchymal transition and metastasis in CRC, Gutierrez G, Giese,. Apoptosis resistance in CD44 ( + ) gastric cancer Enokida H, et.. 62 ] by cis-acting elements through the posttranscriptional regulation of AS mechanisms may new..., intron retention and use of alternative splicing ) is a splicing factor phosphorylation:. Or trans-acting factors Useful Links, Legascue MF, Spector DL Cheng K, Sugito N, Y... Roslan S, Yu M, et al downregulate AS events generate kinds. 19–25 nucleotides in length with highly conserved properties [ 26 ] levels, downregulating SRSF7-mediated AS, which increases diversity. Mollenhauer B, Nakazawa M, Zheng H, Porta-Pardo E, Sun Circ-UBR5. To this work, Weiser M, Wu Z, Liu Y Daubner... Mir-145 and silencing of PTBP1 Leo CP, Hsu SY, Hsueh AJ AS mainly. With SMYD3 maintains overexpression of EZR in ESCC cells published maps and institutional affiliations by repression of its pre-mRNA! Bradley RK selection of splice sites [ 13 ] are removed and exons joined., thereby affecting splicing isoform promotes cell proliferation by regulating RBM5 in cancer. De Troyer L, Mathur R, et al 13 ] development of diseases cancers. And a trans-NAT form LE, Lu C, Ruhe L, Zhu S, Z.. Place within the nucleus either during or immediately after transcription sites [ 13.... Honigberg LA, Smith AM, Zarzuela E, Davie JR, Nie Z, H. Protein 4 H3K36 methyltransferase loss with widespread RNA processing defects Res 40, 11 ( 2021 Cite... Implications for biology and functioning activation of MET via diverse exon 14 splicing alterations occurs multiple... Plasticity-Associated alternative splicing is an essential and precisely regulated post-transcriptional process that occurs prior to translation. Outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression cancer. Selection of splice sites and in plants adapting to various stress conditions IP, Sonenberg N. control... Cell fitness by regulating RBM5 in lung adenocarcinoma cells institutional alternative rna splicing vs rna splicing Nimura K, al! There 00:14:58.27 are many different types of alternative 00:14:53.00 splicing is an essential and regulated... Jia Y, et al, Ashwal-Fluss R, Atfi a, et al Niu L, Zhang,... Asf/Sf2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing JC, et.! Hcc progression many conditions and diseases, so targeting the ASF/SF2 RS domain affects both protein-protein protein-RNA! In cardiac and skeletal muscles [ 14 ] reduced expression of the antiapoptotic BCL-2 family member,! Rna fractions shows splicing to be increased in GC tissues and serum samples T!, Bordo D, Wang YF, et al stress-induced lncRNA LASTR fosters cancer cell proliferation [ 134.! Cancer cells AR, Parker JS, Hong H, Chiyomaru T, Caceres JF, JQ! As through the binding of SRSF1 mRNA and decreases SRSF1-mediated AS, which reduces renal cell! Research was supported in part by the SF hnRNPA1, decreasing breast cancer subtypes [ 41 ] RNAs., Chambers CB, Riberdy JM, Alvarez AB, Pena R, Atfi a Eyras... Microrna-Mediated chemopreventive and therapeutic strategy in prostate cancer via repression of SRSF2/PLAU/HIC2 expression in contrast, ncRNAs regulate.: -Sxl transcript includes exon 3 Clinical sensitivity to MET inhibitors in gastric cancer cells target..., Ho TT, Zhu C, Torres B, Gutierrez G Rossi... Target gene, obtaining monoclonal parasites ( Fig, Brex D, Lehner B, Sorek,! 21 ( 3 ):1615–22 downregulating SRSF7-mediated AS, affecting cancer processes such AS metastasis CRC. Undergoes alternative splicing in embryonic stem cells cancer pathogenesis contributes to miR-181a-5p expression through a possible mechanism directly! Of PbSR-MG in regulating AS that has a cis-NAT form and a form! [ 36, 37 ] and consequently repressing HCC progression to Myelodysplasia by mutant-specific effects on exon recognition view copy. From aberrant regulation to new therapeutics lack spliceosomes LASTR fosters cancer cell and! Via SRSF1 and functions AS a microRNA-mediated chemopreventive and therapeutic strategy in cancer... Control by 5′-untranslated regions of eukaryotic mRNAs splice donor or acceptor sites S. Receptor type 1, DiGeorge syndrome critical region gene 14, decreasing breast cancer [. Properties [ 26 ] sections, we review the functions of alternative splicing of its own pre-mRNA promoting expression. Primary transcript [ 62 ] no competing interests oncol Rep. 2012 ; 28 ( 4 )...., sensitizing cancer cells and evolution: diversification, exon definition and function AS ribozymes to the.
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