Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes

Funan He1, Ran Wei1, Zhan Zhou2

  • 1Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200433, China.

Scientific Reports
|June 5, 2019
PubMed

Insights

Single-nucleotide variations altering RNA secondary structure (riboSNitches) are linked to human diseases. Our study introduces SNIPER to identify riboSNitches in cancer genomes, revealing their pathogenic potential and association with cancer-related noncoding elements.

Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • RNA secondary structure influences critical cellular processes like RNA processing, stability, localization, and translation.
  • Single-nucleotide variations (SNVs) that disrupt RNA secondary structure, termed riboSNitches, are implicated in human diseases, particularly within untranslated regions (UTRs) and noncoding RNAs (ncRNAs).
  • The role of somatic mutations acting as riboSNitches in cancer development is not well understood.

Purpose of the Study:

  • To develop a computational pipeline, SNIPER, for detecting riboSNitches in cancer genomes.
  • To identify non-coding elements significantly enriched or depleted of riboSNitches in tumors.
  • To investigate the potential pathogenicity and cancer relevance of riboSNitches.

Main Methods:

  • Development of the SNIPER (riboSNitch-enriched or depleted elements in cancer genomes) computational pipeline.
  • Utilizing MeanDiff and EucDiff algorithms within SNIPER to detect riboSNitches.
  • Analysis of cancer genomes to identify enriched or depleted riboSNitch non-coding elements.

Main Results:

  • RiboSNitches were found to be more likely pathogenic.
  • Identification of specific UTRs and long non-coding RNAs (lncRNAs) significantly enriched or depleted of riboSNitches in cancer genomes.
  • These findings suggest potential roles for these elements as cancer drivers or essential noncoding components.

Conclusions:

  • RNA secondary structure plays a potentially overlooked role in cancer genomes.
  • The SNIPER pipeline offers a novel strategy for identifying cancer-associated genes through riboSNitch analysis.
  • This research highlights the importance of considering RNA structural variations in cancer etiology.

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