Uncovering the translation potential of SNHG5, a long non-coding RNA in colorectal cancer

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Date
2021-07-01
Authors
Hurley, Cian
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University College Cork
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Abstract
Colorectal (bowel) cancer (CRC) is one of the most common types of cancer worldwide, with an estimated 1.8 million cases in 2018 (World Health Organization). Long, non-coding RNAs (lncRNAs) are transcribed, but not translated efficiently into proteins. With advances in sequencing technologies, lncRNAs have emerged as regulators of normal cellular events and disease states, including CRC. One lncRNA specifically associated with CRC is small, nucleolar, RNA host human gene 5 – SNHG5. Downregulation of the SNHG5 lncRNA in colorectal cancer causes apoptosis and cell cycle arrest, as well as limiting tumour growth. Conversely, lncRNA overexpression increased tumour cell resistance to oxaliplatin-induced apoptosis. Previous studies attributed these functions to the lncRNA molecule itself, determining that there was no coding potential within the SNHG5 lncRNA. However, upon close examination of published data, we believe that the SNHG5 RNA is occupied by one or two translating ribosomes and have discovered a small open reading frame (sORF) that encodes a 35 amino acid microprotein within the transcript. Evidence from ribosome profiling, sequence conservation, Kozak context, and early experimental data with tagged constructs all support the hypothesis that an SNHG5 microprotein may exist. This work provides an exciting new avenue to consider the SNHG5 microprotein as a biomarker of CRC that could be harnessed for diagnostic or prognostic clinical applications.
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lncRNA , RNA , Colorectal cancer , Translation
Citation
Hurley, C. 2021. Uncovering the translation potential of SNHG5, a long non-coding RNA in colorectal cancer. MRes Thesis, University College Cork.