High-throughput Interrogation of Programmed Ribosomal Frameshifting in Human Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jun 18

PMID 32546731

Citations 14

Authors

Martin Mikl

Yitzhak Pilpel

Eran Segal

Affiliations

Soon will be listed here.

Abstract

Programmed ribosomal frameshifting (PRF) is the controlled slippage of the translating ribosome to an alternative frame. This process is widely employed by human viruses such as HIV and SARS coronavirus and is critical for their replication. Here, we developed a high-throughput approach to assess the frameshifting potential of a sequence. We designed and tested >12,000 sequences based on 15 viral and human PRF events, allowing us to systematically dissect the rules governing ribosomal frameshifting and discover novel regulatory inputs based on amino acid properties and tRNA availability. We assessed the natural variation in HIV gag-pol frameshifting rates by testing >500 clinical isolates and identified subtype-specific differences and associations between viral load in patients and the optimality of PRF rates. We devised computational models that accurately predict frameshifting potential and frameshifting rates, including subtle differences between HIV isolates. This approach can contribute to the development of antiviral agents targeting PRF.

Citing Articles

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