Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing

Xin Wang, Kejun Wang, Milan Radovich, Yue Wang, Guohua Wang, Weixing Feng, Jeremy R. Sanford, Yunlong Liu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by trans-acting factors that bind on exonic and intronic cis-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify cis-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, SplicingModeler, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues. Results: Using a publicly available Affymetrix Genechip® Human Exon Array dataset, our method identifies 652 cis-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific cis-acting elements and "general elements" whose functional activities are important but differ across multiple tissues. Conclusion: In this study, we present a model-based computational approach to identify potential cis-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple cis-acting regulators. This methodology provides a novel evaluation on the functional levels of cis-acting RNA elements by estimating their tissue-specific functions on various tissues.

Original languageEnglish
Article numberS4
JournalBMC Genomics
Volume10
Issue numberSUPPL. 1
DOIs
StatePublished - Jul 7 2009

Fingerprint

RNA Precursors
Alternative Splicing
Genome
RNA
Exons
Trans-Activators
RNA-Binding Proteins
Nucleic Acid Regulatory Sequences
Protein Binding
Cerebellum
Testis
Binding Sites
Databases

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing. / Wang, Xin; Wang, Kejun; Radovich, Milan; Wang, Yue; Wang, Guohua; Feng, Weixing; Sanford, Jeremy R.; Liu, Yunlong.

In: BMC Genomics, Vol. 10, No. SUPPL. 1, S4, 07.07.2009.

Research output: Contribution to journalArticle

Wang, Xin ; Wang, Kejun ; Radovich, Milan ; Wang, Yue ; Wang, Guohua ; Feng, Weixing ; Sanford, Jeremy R. ; Liu, Yunlong. / Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing. In: BMC Genomics. 2009 ; Vol. 10, No. SUPPL. 1.
@article{356aecda0d874eeb959f521f83e162a6,
title = "Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing",
abstract = "Background: Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by trans-acting factors that bind on exonic and intronic cis-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify cis-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, SplicingModeler, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues. Results: Using a publicly available Affymetrix Genechip{\circledR} Human Exon Array dataset, our method identifies 652 cis-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific cis-acting elements and {"}general elements{"} whose functional activities are important but differ across multiple tissues. Conclusion: In this study, we present a model-based computational approach to identify potential cis-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple cis-acting regulators. This methodology provides a novel evaluation on the functional levels of cis-acting RNA elements by estimating their tissue-specific functions on various tissues.",
author = "Xin Wang and Kejun Wang and Milan Radovich and Yue Wang and Guohua Wang and Weixing Feng and Sanford, {Jeremy R.} and Yunlong Liu",
year = "2009",
month = "7",
day = "7",
doi = "10.1186/1471-2164-10-S1-S4",
language = "English",
volume = "10",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing

AU - Wang, Xin

AU - Wang, Kejun

AU - Radovich, Milan

AU - Wang, Yue

AU - Wang, Guohua

AU - Feng, Weixing

AU - Sanford, Jeremy R.

AU - Liu, Yunlong

PY - 2009/7/7

Y1 - 2009/7/7

N2 - Background: Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by trans-acting factors that bind on exonic and intronic cis-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify cis-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, SplicingModeler, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues. Results: Using a publicly available Affymetrix Genechip® Human Exon Array dataset, our method identifies 652 cis-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific cis-acting elements and "general elements" whose functional activities are important but differ across multiple tissues. Conclusion: In this study, we present a model-based computational approach to identify potential cis-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple cis-acting regulators. This methodology provides a novel evaluation on the functional levels of cis-acting RNA elements by estimating their tissue-specific functions on various tissues.

AB - Background: Human genes undergo various patterns of pre-mRNA splicing across different tissues. Such variation is primarily regulated by trans-acting factors that bind on exonic and intronic cis-acting RNA elements (CAEs). Here we report a computational method to mechanistically identify cis-acting RNA elements that contribute to the tissue-specific alternative splicing pattern. This method is an extension of our previous model, SplicingModeler, which predicts the significant CAEs that contribute to the splicing differences between two tissues. In this study, we introduce tissue-specific functional levels estimation step, which allows evaluating regulatory functions of predicted CAEs that are involved in more than two tissues. Results: Using a publicly available Affymetrix Genechip® Human Exon Array dataset, our method identifies 652 cis-acting RNA elements (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped to the known RBP (RNA binding protein) binding sites or match with other predicted exonic splicing regulator databases. Interestingly, the vast majority of predicted CAEs are in intronic regulatory regions. A noticeable exception is that many exonic elements are found to regulate the alternative splicing between cerebellum and testes. Most identified elements are found to contribute to the alternative splicing between two tissues, while some are important in multiple tissues. This suggests that genome-wide alternative splicing patterns are regulated by a combination of tissue-specific cis-acting elements and "general elements" whose functional activities are important but differ across multiple tissues. Conclusion: In this study, we present a model-based computational approach to identify potential cis-acting RNA elements by considering the exon splicing variation as the combinatorial effects of multiple cis-acting regulators. This methodology provides a novel evaluation on the functional levels of cis-acting RNA elements by estimating their tissue-specific functions on various tissues.

UR - http://www.scopus.com/inward/record.url?scp=67650535956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650535956&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-10-S1-S4

DO - 10.1186/1471-2164-10-S1-S4

M3 - Article

VL - 10

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - SUPPL. 1

M1 - S4

ER -