PUBLICATION

Protein Sam68 regulates the alternative splicing of survivin DEx3

Authors
Gaytan-Cervantes, J., Gonzalez-Torres, C., Maldonado, V., Zampedri, C., Ceballos-Cancino, G., Melendez-Zajgla, J.
ID
ZDB-PUB-170907-11
Date
2017
Source
The Journal of biological chemistry   292: 13745-13757 (Journal)
Registered Authors
Keywords
KHDRBS1, Sam68, alternative splicing, cancer, cancer biology, gene regulation, survivin, survivin DEx3
MeSH Terms
  • Adaptor Proteins, Signal Transducing/antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Alternative Splicing*
  • Animals
  • CRISPR-Cas Systems
  • Clone Cells
  • DNA-Binding Proteins/antagonists & inhibitors
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Embryo, Nonmammalian
  • Exons
  • Gene Deletion
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins/genetics
  • Inhibitor of Apoptosis Proteins/metabolism*
  • Mutagenesis, Site-Directed
  • Neoplasm Proteins/antagonists & inhibitors
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism*
  • Neoplasm Transplantation/pathology
  • Point Mutation
  • Protein Isoforms/antagonists & inhibitors
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • RNA Interference
  • RNA, Messenger/chemistry
  • RNA, Messenger/metabolism*
  • RNA, Neoplasm/chemistry
  • RNA, Neoplasm/metabolism*
  • RNA-Binding Proteins/antagonists & inhibitors
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism*
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/metabolism
  • Response Elements*
  • Transplantation, Heterologous
  • Tumor Burden
  • Zebrafish
PubMed
28655776 Full text @ J. Biol. Chem.
Abstract
Messenger RNA alternative splicing (AS) regulates the expression of a variety of genes involved in both physiological and pathological processes. AS of the anti-apoptotic and proliferation-associated survivin (BIRC5) gene generates six isoforms, which regulate key aspects of cancer initiation and progression. One of the isoforms is survivin DEx3, in which the exclusion of exon 3 generates a unique carboxyl terminus with specific anti-apoptotic functions. This isoform is highly expressed in advanced stages of breast and cervical tumors. Therefore, understanding the mechanisms that regulate survivin DEx3 mRNA AS is clearly important. To this end, we designed a minigene (M), and in combination with a series of deletions and site-directed mutations, we determined that the first 22 bp of exon 3 contain cis-acting elements that enhance the exclusion of exon 3 to generate the survivin DEx3 mRNA isoform. Furthermore, using pulldown assays, we discovered that Sam68 is a possible trans-acting factor that binds to this region and regulates exon 3 splicing. This result was corroborated using a cell line in which the Sam68 binding site in the survivin gene was mutated with the CRISPR/Cas system. This work provides the first clues regarding the regulation of survivin DEx3 mRNA splicing.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping