The role of MERVLs as alternative promoters in ZGA
File(s)
Author(s)
Arya, Srishti
Type
Thesis or dissertation
Abstract
Careful tuning of transcription and translation during embryogenesis, specifically at the initial awakening of the embryonic genome (zygotic genome activation, or ZGA) is crucial for correct embryogenesis. Mouse ZGA, at the 2-cell stage, is hallmarked by the de-repression of murine endogenous retroviruses with leucine primers (MERVLs). Co-option of the MERVLs’ LTRs as alternative promoters has been observed for embryogenesis-related genes. However, no transcriptome-wide studies have been completed specifically for ZGA genes with MERVL alternative promoters yet.
Here, I present an analysis of published long-read RNA-seq data from 2-cell embryos to examine the repertoire of chimeric transcripts promoted by MERVLs, supplemented by short-read RNA-seq data from 2C embryos and 2-cell-like cells (2CLCs). 2CLCs provide an effective in vitro system to study early mouse embryogenesis, due to their emulation of 2-cell stage embryos’ epigenetic, metabolic, and transcriptomic state, with characteristic MERVL expression. I collate a list of 549 high-confidence transcripts promoted by MERVLs, from 167 genes, and assess their expression across preimplantation development. Subsequently, I examine the coding potential of these transcripts, identifying 15 genes with 2C specific transcripts. Of these, 6 genes have MERVL-promoted isoforms with altered protein domains, and therefore, possibly altered functions. This study opens doors to examination of changes in protein domains or signal peptides for MERVL-promoted transcripts, as well as further examination of tertiary protein structure and binding partners using computational and experimental techniques.
Here, I present an analysis of published long-read RNA-seq data from 2-cell embryos to examine the repertoire of chimeric transcripts promoted by MERVLs, supplemented by short-read RNA-seq data from 2C embryos and 2-cell-like cells (2CLCs). 2CLCs provide an effective in vitro system to study early mouse embryogenesis, due to their emulation of 2-cell stage embryos’ epigenetic, metabolic, and transcriptomic state, with characteristic MERVL expression. I collate a list of 549 high-confidence transcripts promoted by MERVLs, from 167 genes, and assess their expression across preimplantation development. Subsequently, I examine the coding potential of these transcripts, identifying 15 genes with 2C specific transcripts. Of these, 6 genes have MERVL-promoted isoforms with altered protein domains, and therefore, possibly altered functions. This study opens doors to examination of changes in protein domains or signal peptides for MERVL-promoted transcripts, as well as further examination of tertiary protein structure and binding partners using computational and experimental techniques.
Version
Open Access
Date Issued
2024-06-05
Date Awarded
2024-08-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Vaquerizas, Juan M.
Sponsor
Medical Research Council (Great Britain)
Publisher Department
Institute of Clinical Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Master of Philosophy (MPhil)