The RNA-binding protein Secisbp2 differentially modulates UGA codon reassignment and RNA decay

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The genetic code's dual-assignment expands its capacity, with UGA codons reassigned for selenocysteine incorporation in mammals.
• This process involves a 3' untranslated region (UTR) selenocysteine insertion sequence (SECIS) and the SECIS-binding protein, Secisbp2.

Purpose of the Study:

• To investigate the distinct roles of Secisbp2 in UGA codon redefinition and mRNA stability.
• To determine if Secisbp2's effects on selenoprotein synthesis are solely due to impaired selenocysteine incorporation.

Main Methods:

• Ribosome profiling, RNA-Seq, and mRNA half-life measurements were employed.
• Conditional gene deletions of Secisbp2 and Trsp (tRNASec) in mouse liver were analyzed.

Main Results:

• tRNASec depletion abolished ribosome density downstream of UGA-Sec codons, as expected.
• Secisbp2 absence showed gene-specific variations in ribosome density, indicating differential Sec incorporation.
• Several selenoproteins exhibited unaffected translation and Sec incorporation despite diminished mRNA levels in Secisbp2-deficient cells.

Conclusions:

• Secisbp2 is not essential for Sec incorporation efficiency.
• Secisbp2 possesses a distinct function in mRNA stabilization, separable from its role in UGA redefinition.