The complexity of human transcriptome is far greater than previously anticipated. Transcript diversity can be expanded through post-transcriptional RNA processing reactions as well as extensive inter-genic transcription. The genomic organization of cisacting RNA elements regulating expression of protein coding genes and non-coding inter-genic transcripts is poorly defined. This deficiency not only hampers our understanding of how the information stored within the human genome is utilized, but also weakens the connections between post-transcriptional control of gene expression and biological processes such as cell proliferation, differentiation and even human disease. The goal of this proposal is to illuminate post-transcriptional networks coordinated by RNA binding proteins. To achieve this goal we will identify cis-acting RNA elements recognized by a complete family of phylogenetically conserved, essential RNA binding proteins on a genome-wide scale. Our application focuses on the Serine and Arginine-rich family of pre-mRNA splicing factors (SR proteins). Biochemical methods will be employed to purify SR protein-RNA complexes under conditions that preserve the physiological context of RNA-protein interactions in the intact cell. Copurifying RNA molecules will be directly identified by two independent high throughput methods, pyrosequencing and hybridization to tiled genomic microarrays. Our R01 application will address the following specific aims: (1) Comprehensively identify cis-acting RNA elements recognized by the SR protein family. (2) Determine the genomic landscape of cis-acting RNA elements recognized by SR proteins. (3) Functionally validate SR protein cis-acting RNA elements.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Bender, Michael T
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Santa Cruz
Schools of Arts and Sciences
Santa Cruz
United States
Zip Code
Rice, Edward S; Kohno, Satomi; John, John St et al. (2017) Improved genome assembly of American alligator genome reveals conserved architecture of estrogen signaling. Genome Res 27:686-696
Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy et al. (2016) IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC. Cell Rep 15:1876-83
Roberts, Jacqueline M; Ennajdaoui, Hanane; Edmondson, Carina et al. (2014) Splicing factor TRA2B is required for neural progenitor survival. J Comp Neurol 522:372-92
Sterne-Weiler, Timothy; Martinez-Nunez, Rocio Teresa; Howard, Jonathan M et al. (2013) Frac-seq reveals isoform-specific recruitment to polyribosomes. Genome Res 23:1615-23
Uren, Philip J; Bahrami-Samani, Emad; Burns, Suzanne C et al. (2012) Site identification in high-throughput RNA-protein interaction data. Bioinformatics 28:3013-20
Zhou, Ao; Breese, Marcus R; Hao, Yangyang et al. (2012) Alt Event Finder: a tool for extracting alternative splicing events from RNA-seq data. BMC Genomics 13 Suppl 8:S10
St John, John A; Braun, Edward L; Isberg, Sally R et al. (2012) Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes. Genome Biol 13:415
Teng, Mingxiang; Wang, Yadong; Wang, Guohua et al. (2011) Prioritizing single-nucleotide variations that potentially regulate alternative splicing. BMC Proc 5 Suppl 9:S40
Sterne-Weiler, Timothy; Howard, Jonathan; Mort, Matthew et al. (2011) Loss of exon identity is a common mechanism of human inherited disease. Genome Res 21:1563-71
Wang, Xin; Juan, Liran; Lv, Junjie et al. (2011) Predicting sequence and structural specificities of RNA binding regions recognized by splicing factor SRSF1. BMC Genomics 12 Suppl 5:S8

Showing the most recent 10 out of 15 publications