Regulating gene expression through RNA nuclear retention

Kannanganattu V. Prasanth, Supriya G. Prasanth, Zhenyu Xuan, Stephen Hearn, Susan M. Freier, C. Frank Bennett, Michael Q. Zhang, David L. Spector

Research output: Contribution to journalArticle

Abstract

Multiple mechanisms have evolved to regulate the eukaryotic genome. We have identified CTN-RNA, a mouse tissue-specific ∼8 kb nuclear-retained poly(A)+ RNA that regulates the level of its protein-coding partner. CTN-RNA is transcribed from the protein-coding mouse cationic amino acid transporter 2 (mCAT2) gene through alternative promoter and poly(A) site usage. CTN-RNA is diffusely distributed in nuclei and is also localized to paraspeckles. The 3′UTR of CTN-RNA contains elements for adenosine-to-inosine editing, involved in its nuclear retention. Interestingly, knockdown of CTN-RNA also downregulates mCAT2 mRNA. Under stress, CTN-RNA is posttranscriptionally cleaved to produce protein-coding mCAT2 mRNA. Our findings reveal a role of the cell nucleus in harboring RNA molecules that are not immediately needed to produce proteins but whose cytoplasmic presence is rapidly required upon physiologic stress. This mechanism of action highlights an important paradigm for the role of a nuclear-retained stable RNA transcript in regulating gene expression.

Original languageEnglish (US)
Pages (from-to)249-263
Number of pages15
JournalCell
Volume123
Issue number2
DOIs
StatePublished - Oct 21 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Prasanth, K. V., Prasanth, S. G., Xuan, Z., Hearn, S., Freier, S. M., Bennett, C. F., Zhang, M. Q., & Spector, D. L. (2005). Regulating gene expression through RNA nuclear retention. Cell, 123(2), 249-263. https://doi.org/10.1016/j.cell.2005.08.033