CFIm25 links alternative polyadenylation to glioblastoma tumour suppression

Chioniso P. Masamha, Zheng Xia, Jingxuan Yang, Todd R. Albrecht, Min Li, Ann Bin Shyu, Wei Li, Eric Wagner

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

The global shortening of messenger RNAs through alternative polyadenylation (APA) that occurs during enhanced cellular proliferation represents an important, yet poorly understood mechanism of regulated gene expression. The 3′ untranslated region (UTR) truncation of growth-promoting mRNA transcripts that relieves intrinsic microRNA- and AU-rich-element-mediated repression has been observed to correlate with cellular transformation; however, the importance to tumorigenicity of RNA 3′-end-processing factors that potentially govern APA is unknown. Here we identify CFIm25 as a broad repressor of proximal poly(A) site usage that, when depleted, increases cell proliferation. Applying a regression model on standard RNA-sequencing data for novel APA events, we identified at least 1,450 genes with shortened 3′ UTRs after CFIm25 knockdown, representing 11% of significantly expressed mRNAs in human cells. Marked increases in the expression of several known oncogenes, including cyclin D1, are observed as a consequence of CFIm25 depletion. Importantly, we identified a subset of CFIm25-regulated APA genes with shortened 3′ UTRs in glioblastoma tumours that have reduced CFIm25 expression. Downregulation of CFIm25 expression in glioblastoma cells enhances their tumorigenic properties and increases tumour size, whereas CFIm25 overexpression reduces these properties and inhibits tumour growth. These findings identify a pivotal role of CFIm25 in governing APA and reveal a previously unknown connection between CFIm25 and glioblastoma tumorigenicity.

Original languageEnglish (US)
Pages (from-to)412-416
Number of pages5
JournalNature
Volume510
Issue number7505
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Polyadenylation
Glioblastoma
3' Untranslated Regions
Neoplasms
RNA 3' End Processing
Messenger RNA
AU Rich Elements
Cell Proliferation
RNA Sequence Analysis
Poly A
Cyclin D1
Growth
MicroRNAs
Oncogenes
Genes
Down-Regulation
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Masamha, C. P., Xia, Z., Yang, J., Albrecht, T. R., Li, M., Shyu, A. B., ... Wagner, E. (2014). CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature, 510(7505), 412-416. https://doi.org/10.1038/nature13261

CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. / Masamha, Chioniso P.; Xia, Zheng; Yang, Jingxuan; Albrecht, Todd R.; Li, Min; Shyu, Ann Bin; Li, Wei; Wagner, Eric.

In: Nature, Vol. 510, No. 7505, 2014, p. 412-416.

Research output: Contribution to journalArticle

Masamha, CP, Xia, Z, Yang, J, Albrecht, TR, Li, M, Shyu, AB, Li, W & Wagner, E 2014, 'CFIm25 links alternative polyadenylation to glioblastoma tumour suppression', Nature, vol. 510, no. 7505, pp. 412-416. https://doi.org/10.1038/nature13261
Masamha CP, Xia Z, Yang J, Albrecht TR, Li M, Shyu AB et al. CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature. 2014;510(7505):412-416. https://doi.org/10.1038/nature13261
Masamha, Chioniso P. ; Xia, Zheng ; Yang, Jingxuan ; Albrecht, Todd R. ; Li, Min ; Shyu, Ann Bin ; Li, Wei ; Wagner, Eric. / CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. In: Nature. 2014 ; Vol. 510, No. 7505. pp. 412-416.
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