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PRPF19 mRNA Encodes a Small Open Reading Frame That Is Important for Viability of Human Cells.

N M Shepelev1,2, A O Kurochkina2, O A Dontsova1,2,3,4

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Summary

Thousands of small upstream open reading frames (uORFs) in messenger RNAs are translated, regulating gene expression or forming microproteins. We found a translated uORF in PRPF19 mRNA that is essential for human cell viability.

Keywords:
micropeptidemicroproteinribosome profilinguORFupstream ORF

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Messenger RNAs (mRNAs) contain 5' untranslated regions (UTRs) that can harbor small open reading frames (uORFs).
  • These uORFs are increasingly recognized for their roles in regulating gene expression and potentially encoding functional microproteins.

Purpose of the Study:

  • To investigate the translational activity of uORFs within the 5' UTR of human PRPF19 mRNA.
  • To determine the functional significance of this specific uORF in human cells.

Main Methods:

  • High-throughput ribosome profiling was employed to identify translated uORFs.
  • Genetic manipulation was used to inactivate the identified uORF in PRPF19 mRNA.

Main Results:

  • Demonstrated the translation of a uORF within the 5' UTR of human PRPF19 mRNA.
  • Inactivation of this PRPF19 uORF led to a significant reduction in human cell viability.

Conclusions:

  • The 5' UTR of PRPF19 mRNA encodes a translatable uORF.
  • This uORF plays a critical role in maintaining human cell viability, highlighting its essential function.