Identification of diverse target RNAs that are functionally regulated by human pumilio proteins

Jennifer A. Bohn, Jamie L. Van Etten, Trista L. Schagat, Brittany M. Bowman, Richard C. McEachin, Peter L. Freddolino, Aaron Goldstrohm

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Human Pumilio proteins, PUM1 and PUM2, are sequence specific RNA-binding proteins that regulate protein expression. We used RNA-seq, rigorous statistical testing and an experimentally derived fold change cut-off to identify nearly 1000 target RNAs––including mRNAs and non-coding RNAs––that are functionally regulated by PUMs. Bioinformatic analysis defined a PUM Response Element (PRE) that was significantly enriched in transcripts that increased in abundance and matches the PUM RNA-binding consensus. We created a computational model that incorporates PRE position and frequency within an RNA relative to the magnitude of regulation. The model reveals significant correlation of PUM regulation with PREs in 3 untranslated regions (UTRs), coding sequences and noncoding RNAs, but not 5 UTRs. To define direct, high confidence PUM targets, we cross-referenced PUM-regulated RNAs with all PRE-containing RNAs and experimentally defined PUM-bound RNAs. The results define nearly 300 direct targets that include both PUM-repressed and, surprisingly, PUM-activated target RNAs. Annotation enrichment analysis reveal that PUMs regulate genes from multiple signaling pathways and developmental and neurological processes. Moreover, PUM target mRNAs impinge on human disease genes linked to cancer, neurological disorders and cardiovascular disease. These discoveries pave the way for determining how the PUM-dependent regulatory network impacts biological functions and disease states.

Original languageEnglish (US)
Pages (from-to)362-386
Number of pages25
JournalNucleic acids research
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2018

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RNA
Response Elements
Untranslated RNA
Messenger RNA
RNA-Binding Proteins
5' Untranslated Regions
3' Untranslated Regions
human pumilio protein
Nervous System Diseases
Computational Biology
Genes
Cardiovascular Diseases
Neoplasms
Proteins

PubMed: MeSH publication types

  • Journal Article

Cite this

Bohn, J. A., Van Etten, J. L., Schagat, T. L., Bowman, B. M., McEachin, R. C., Freddolino, P. L., & Goldstrohm, A. (2018). Identification of diverse target RNAs that are functionally regulated by human pumilio proteins. Nucleic acids research, 46(1), 362-386. https://doi.org/10.1093/nar/gkx1120

Identification of diverse target RNAs that are functionally regulated by human pumilio proteins. / Bohn, Jennifer A.; Van Etten, Jamie L.; Schagat, Trista L.; Bowman, Brittany M.; McEachin, Richard C.; Freddolino, Peter L.; Goldstrohm, Aaron.

In: Nucleic acids research, Vol. 46, No. 1, 01.01.2018, p. 362-386.

Research output: Contribution to journalArticle

Bohn, JA, Van Etten, JL, Schagat, TL, Bowman, BM, McEachin, RC, Freddolino, PL & Goldstrohm, A 2018, 'Identification of diverse target RNAs that are functionally regulated by human pumilio proteins' Nucleic acids research, vol. 46, no. 1, pp. 362-386. https://doi.org/10.1093/nar/gkx1120
Bohn JA, Van Etten JL, Schagat TL, Bowman BM, McEachin RC, Freddolino PL et al. Identification of diverse target RNAs that are functionally regulated by human pumilio proteins. Nucleic acids research. 2018 Jan 1;46(1):362-386. https://doi.org/10.1093/nar/gkx1120
Bohn, Jennifer A. ; Van Etten, Jamie L. ; Schagat, Trista L. ; Bowman, Brittany M. ; McEachin, Richard C. ; Freddolino, Peter L. ; Goldstrohm, Aaron. / Identification of diverse target RNAs that are functionally regulated by human pumilio proteins. In: Nucleic acids research. 2018 ; Vol. 46, No. 1. pp. 362-386.
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