Massively Parallel Jumping Assay Decodes Retrotransposition Activity

Overview

Journal bioRxiv

Date 2024 Apr 25

PMID 38659854

Authors

Navneet Matharu

Jingjing Zhao

Ajuni Sohota

Linbei Deng

Yan Hung

Zizheng Li

Jasmine Sims

Sawitree Rattanasopha

Josh Meyer

Lucia Carbone

Martin Kircher

Nadav Ahituv

Affiliations

Soon will be listed here.

Abstract

The human genome contains millions of retrotransposons, several of which could become active due to somatic mutations having phenotypic consequences, including disease. However, it is not thoroughly understood how nucleotide changes in retrotransposons affect their jumping activity. Here, we developed a novel massively parallel jumping assay (MPJA) that can test the jumping potential of thousands of transposons . We generated nucleotide variant library of selected four retrotransposons containing 165,087 different haplotypes and tested them for their jumping ability using MPJA. We found 66,821 unique jumping haplotypes, allowing us to pinpoint domains and variants vital for transposition. Mapping these variants to the -RNA secondary structure revealed stem-loop features that contribute to jumping potential. Combined, our work provides a novel high-throughput assay that assesses the ability of retrotransposons to jump and identifies nucleotide changes that have the potential to reactivate them in the human genome.

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