Abstract
Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3205-3211 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 503 |
| Issue number | 4 |
| DOIs | |
| State | Published - Sep 18 2018 |
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Keywords
- Alternative splicing
- CELF1
- Diabetic heart
- RNA binding proteins
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart. / Belanger, Karry Anne; Nutter, Curtis A.; Li, Jin; Tasnim, Sadia; Liu, Peiru; Yu, Peng; Martinez, Neslihan.
In: Biochemical and Biophysical Research Communications, Vol. 503, No. 4, 18.09.2018, p. 3205-3211.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart
AU - Belanger, Karry Anne
AU - Nutter, Curtis A.
AU - Li, Jin
AU - Tasnim, Sadia
AU - Liu, Peiru
AU - Yu, Peng
AU - Martinez, Neslihan
PY - 2018/9/18
Y1 - 2018/9/18
N2 - Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.
AB - Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.
KW - Alternative splicing
KW - CELF1
KW - Diabetic heart
KW - RNA binding proteins
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UR - http://www.scopus.com/inward/citedby.url?scp=85052863867&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2018.08.126
DO - 10.1016/j.bbrc.2018.08.126
M3 - Article
C2 - 30158053
AN - SCOPUS:85052863867
VL - 503
SP - 3205
EP - 3211
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -