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Identification of Functional Protein Regions Through Chimeric Protein Construction

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Ribosomal frameshifting at normal codon repeats recodes functional chimeric proteins in human.

Guiping Ren^1,2, Xiaoqian Gu^1,2, Lu Zhang^1,2

¹State Key Laboratory for Conservation and Utilization of Bio-Resource in Yunnan, Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Science, School of Life Sciences, Yunnan University, Kunming 650021, China.

Nucleic Acids Research

|January 28, 2024

Summary

Scientists discovered codon repeats stimulate ribosomal frameshifting in humans, producing novel trans-frame proteins. One such protein, HDAC1-FS, impacts cell migration and apoptosis, suggesting a new layer of gene regulation.

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Area of Science:

Molecular Biology
Genetics
Biochemistry

Background:

Ribosomal frameshifting is a known mechanism in viruses and bacteria for producing essential proteins.
Functional trans-frame proteins resulting from ribosomal frameshifting are rarely documented in humans.
Understanding novel gene expression mechanisms is crucial for human biology.

Purpose of the Study:

To investigate the role of codon repeats in stimulating ribosomal frameshifting in human cells.
To identify and characterize novel trans-frame proteins generated by this mechanism.
To elucidate the functional significance of these trans-frame proteins in human physiology.

Main Methods:

Utilized multiple biochemical and genetic assays to detect and analyze ribosomal frameshifting.
Employed proteomic analyses across 32 normal human tissues to identify trans-frame peptides.
Performed functional assays to determine the biological impact of a specific trans-frame protein (HDAC1-FS).

Main Results:

Identified short codon repeats as cis-acting elements that promote ribosomal frameshifting in humans (CRFS).
Discovered numerous putative CRFS events in normal human tissues, supported by trans-frame peptides.
Demonstrated that the CRFS-derived HDAC1-FS protein antagonizes HDAC1 activity, affecting cell migration and apoptosis.

Conclusions:

Codon repeats represent a novel mechanism for translational recoding in humans.
This process expands the coding capacity of messenger RNA (mRNA).
CRFS contributes to diversifying gene regulation and protein function in human cells.