scholarly journals Alternative mRNA splicing of SAP30L regulates its transcriptional repression activity

FEBS Letters ◽  
2007 ◽  
Vol 582 (2) ◽  
pp. 379-384 ◽  
Author(s):  
Hanna Korkeamäki ◽  
Keijo Viiri ◽  
Mari K. Kukkonen ◽  
Markku Mäki ◽  
Olli Lohi
Keyword(s):  
Transcriptional Repression ◽  
Mrna Splicing ◽  
Alternative Mrna Splicing

scholarly journals Corepressors: Custom Tailoring and Alterations While you Wait

2005 ◽  
Vol 3 (1) ◽  
pp. nrs.03003 ◽  
Author(s):  
Michael Goodson ◽  
Brian A. Jonas ◽  
Martin A. Privalsky
Keyword(s):  
Transcription Factor ◽  
Transcriptional Repression ◽  
Developmental Stages ◽  
Thyroid Hormone Receptor ◽  
Protein Complexes ◽  
Biological Properties ◽  
Mrna Splicing ◽  
Alternative Mrna Splicing ◽  
Splicing Variants ◽  
Protein Variants

A diverse cadre of metazoan transcription factors mediate repression by recruiting protein complexes containing the SMRT (silencing mediator of retinoid and thyroid hormone receptor) or N-CoR (nuclear receptor corepressor) corepressors. SMRT and N-CoR nucleate the assembly of still larger corepressor complexes that perform the specific molecular incantations necessary to confer transcriptional repression. Although SMRT and N-CoR are paralogs and possess similar molecular architectures and mechanistic strategies, they nonetheless exhibit distinct molecular and biological properties. It is now clear that the functions of both SMRT and N-CoR are further diversified through alternative mRNA splicing, yielding a series of corepressor protein variants that participate in distinctive transcription factor partnerships and display distinguishable repression properties. This review will discuss what is known about the structure and actions of SMRT, N-CoR, and their splicing variants, and how alternative splicing may allow the functions of these corepressors to be adapted and tailored to different cells and to different developmental stages.

scholarly journals Corepressor diversification by alternative mRNA splicing is species specific

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Martin L. Privalsky ◽  
Chelsea A. Snyder ◽  
Michael L. Goodson
Keyword(s):  
Mrna Splicing ◽  
Alternative Mrna Splicing ◽  
Species Specific

scholarly journals Asynchronous regulation of splicing events within protein 4.1 pre-mRNA during erythroid differentiation

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3934-3941 ◽  
Author(s):  
F Baklouti ◽  
SC Huang ◽  
TK Tang ◽  
J Delaunay ◽  
VT Marchesi ◽  
...  
Keyword(s):  
Erythroid Differentiation ◽  
Mrna Splicing ◽  
Actin Binding ◽  
Splice Acceptor Site ◽  
Erythroid Cell ◽  
Junctional Complex ◽  
Mrna Isoforms ◽  
Exon 2 ◽  
Protein 4.1 ◽  
Alternative Mrna Splicing

Protein 4.1 is an 80-kD structural component of the red blood cell (RBC) cytoskeleton. It is critical for the formation of the spectrin/actin/protein 4.1 junctional complex, the integrity of which is important for the horizontal strength and elasticity of RBCs. We and others have previously shown that multiple protein 4.1 mRNA isoforms are generated from a single genomic locus by several alternative mRNA splicing events, leading to the insertion or skipping of discrete internal sequence motifs. The physiologic significance of these motifs: (1) an upstream 17-nucleotide sequence located at the 5′ end of exon 2 that contains an in-frame ATG initiation codon, the inclusion of which by use of an alternative splice acceptor site in exon 2 allows the production of a 135-kD high-molecular-weight isoform present in nonerythroid cells; (2) exon 16, which encodes a 21-amino acid (21aa) segment located in the 10-kD “spectrin/actin binding domain” (SAB), the presence of which is required for junctional complex stability in RBCs. Previous studies by our group and others suggested that, among blood cells, this exon was retained only in mature mRNA in the erythroid lineage. Exon 16 is one of a series of three closely linked alternatively spliced exons, generating eight possible mRNA products with unique configurations of the SAB. In this communication, we report studies of the expression of both the translation initiation region and the SAB region during induced erythroid maturation in mouse erythroleukemia (MEL) cells. We have found that only two of eight possible combinatorial patterns of exon splicing at the SAB region are encountered: the isoform lacking all three exons, present in predifferentiated cells, and the isoform containing only exon 16, which increases in amount during erythroid differentiation. The protein isoform containing the 21aa segment encoded by exon 16 efficiently and exclusively incorporates into the membrane, whereas the isoform lacking this 21aa segment remains in the cytoplasm, as well as the membrane. In contrast with exon 16, the erythroid pattern of exon 2 splicing, i.e., skipping of the 17-base sequence at the 5′ end, was found to be already established in the uninduced MEL cells, suggesting strongly that this regulated splicing event occurs at an earlier stage of differentiation. Our results demonstrate asynchronous regulation of two key mRNA splicing events during erythroid cell maturation. These findings also show that the splicing of exon 16 alters the intracellular localization of protein 4.1 in MEL cells, and appears to be essential for its targeting to the plasmalemma.

scholarly journals Analysis of relapse-associated alternative mRNA splicing and construction of a prognostic signature predicting relapse in I–III colon cancer

Genomics ◽  
2020 ◽  
Vol 112 (6) ◽  
pp. 4032-4040 ◽  
Author(s):  
Zhiyuan Zhang ◽  
Qingyang Feng ◽  
Caiwei Jia ◽  
Peng Zheng ◽  
Yang Lv ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mrna Splicing ◽  
Prognostic Signature ◽  
Alternative Mrna Splicing

scholarly journals Identification of a Novel Estrogen Receptor-α Variant and Its Upstream Splicing Regulator

2010 ◽  
Vol 24 (5) ◽  
pp. 914-922 ◽  
Author(s):  
Kazufumi Ohshiro ◽  
Prakriti Mudvari ◽  
Qing-chang Meng ◽  
Suresh K. Rayala ◽  
Aysegul A. Sahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Alternative Splicing ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Α ◽  
Mrna Splicing ◽  
Human Breast ◽  
Alternative Mrna Splicing

Abstract Alternative splicing of precursor mRNA is a fundamental mechanism to generate multiple proteins from a single gene. Although constitutive and alternative mRNA splicing is temporally and spatially regulated, deregulation of mRNA splicing could cause development, progression, and metastasis of tumors. Through yeast two-hybrid screening of a human breast cDNA library using estrogen receptor-α (ERα) as bait, we identified a novel nuclear receptor box containing full-length protein, nuclear protein E3-3 (NPE3-3). Our results revealed that NPE3-3 associates with not only ERα but also with splicing factors, serine/arginine-rich protein (SRp)-30c, SRp40, and splicing factor SC-35, suggesting that NPE3-3 is likely to be involved in regulation of mRNA splicing. Accordingly, transient expression of NPE3-3 in cells resulted in expected splicing of the CD44 control minigene. We also discovered that NPE3-3-overexpressing clones produced a novel, previously unrecognized, alternatively spliced variant of ERα (termed ERαV), which had a molecular size of 37 kDa composed of only exons 1, 2, 7, and 8. ERαV was expressed and sequestered in the cytoplasm in MCF-7 cells stably overexpressing NPE3-3, suggesting its involvement in nongenomic hormone signaling. NPE3-3 clones exhibited up-regulation of ERK1/2 signaling, cyclin D1, and cathepsin D and enhanced tumor cell proliferation, migration, and tumorigenicity. Moreover, direct expression of the ERαV in breast cancer cells stimulated ERK1/2 up-regulation and cyclin D1 expression. We found that ERαV physically interacted with MAPK kinase (MEK)-1/2, and thus, an ERαV and MEK1/2 complex could lead to the activation of the ERK1/2 pathway. Interestingly, NPE3-3 was up-regulated in human breast tumors. These findings revealed a role for NPE3-3 in alternative splicing and suggest that ERα is a physiological target of NPE3-3, leading to a constitutive nongenomic signaling pathway in breast cancer cells.

Sign in / Sign up

Export Citation Format

Share Document