Loss of m(1)acp(3)Ψ ribosomal RNA modification is a major feature of cancer

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Item Type:

Article

Title:

Loss of m(1)acp(3)Ψ ribosomal RNA modification is a major feature of cancer

Creators Name:

Babaian, A. and Rothe, K. and Girodat, D. and Minia, I. and Djondovic, S. and Milek, M. and Spencer Miko, S.E. and Wieden, H.J. and Landthaler, M. and Morin, G.B. and Mager, D.L.

Abstract:

The ribosome is an RNA-protein complex that is essential for translation in all domains of life. The structural and catalytic core of the ribosome is its ribosomal RNA (rRNA). While mutations in ribosomal protein (RP) genes are known drivers of oncogenesis, oncogenic rRNA variants have remained elusive. We identify a cancer-specific single-nucleotide variation in 18S rRNA at nucleotide 1248.U in up to 45.9% of patients with colorectal carcinoma (CRC) and present across >22 cancer types. This is the site of a unique hyper-modified base, 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (m(1)acp(3)Ψ), a >1-billion-years-conserved RNA modification at the peptidyl decoding site of the ribosome. A subset of CRC tumors we call hypo-m(1)acp(3)Ψ shows sub-stoichiometric m(1)acp(3)Ψ modification, unlike normal control tissues. An m(1)acp(3)Ψ knockout model and hypo-m(1)acp(3)Ψ patient tumors share a translational signature characterized by highly abundant ribosomal proteins. Thus, m(1)acp(3)Ψ-deficient rRNA forms an uncharacterized class of "onco-ribosome" which may serve as a chemotherapeutic target for treating cancer patients.

Keywords:

Ribosome, RNA Modification, Ribosomal RNA, rRNA Variation, Ribosomal Heterogeneity, Onco-Ribosome, Cancer, Colorectal Carcinoma, Diffuse Large B-Cell Lymphoma

Source:

Cell Reports

ISSN:

2211-1247

Publisher:

Cell Press / Elsevier

Volume:

Number:

Page Range:

107611

Date:

5 May 2020