Spatiotemporal analysis of mRNA-protein relationships enhances transcriptome-based developmental inference

Cell Rep. 2024 Mar 26;43(3):113928. doi: 10.1016/j.celrep.2024.113928. Epub 2024 Mar 8.

Abstract

Elucidating the complex relationships between mRNA and protein expression at high spatiotemporal resolution is critical for unraveling multilevel gene regulation and enhancing mRNA-based developmental analyses. In this study, we conduct a single-cell analysis of mRNA and protein expression of transcription factors throughout C. elegans embryogenesis. Initially, cellular co-presence of mRNA and protein is low, increasing to a medium-high level (73%) upon factoring in delayed protein synthesis and long-term protein persistence. These factors substantially affect mRNA-protein concordance, leading to potential inaccuracies in mRNA-reliant gene detection and specificity characterization. Building on the learned relationship, we infer protein presence from mRNA expression and demonstrate its utility in identifying tissue-specific genes and elucidating relationships between genes and cells. This approach facilitates identifying the role of sptf-1/SP7 in neuronal lineage development. Collectively, this study provides insights into gene expression dynamics during rapid embryogenesis and approaches for improving the efficacy of transcriptome-based developmental analyses.

Keywords: CP: Developmental biology; cell state analysis; embryogenesis; gene expression specificity; mRNA-protein correlation; post-transcriptional regulation; protein expression inference; protein half-life; single-cell analysis; time-series analysis.

MeSH terms

  • Animals
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spatio-Temporal Analysis
  • Transcription Factors / metabolism
  • Transcriptome* / genetics

Substances

  • RNA, Messenger
  • Transcription Factors