Misfolded human tRNA isodecoder binds and neutralizes a 3' UTR-embedded Alu element.

Area of Science:

• Molecular Biology
• RNA Biology
• Gene Regulation

Background:

• Small noncoding RNAs play crucial roles in cellular metabolism, affecting mRNA decoding, processing, and stability.
• Transfer RNAs (tRNAs) and Alu RNAs are well-characterized RNA classes with diverse cellular functions.

Purpose of the Study:

• To investigate the interaction between a specific tRNA-derived sequence and an Alu RNA element within the 3' UTR of human aspartyl-tRNA synthetase mRNA.
• To elucidate the regulatory mechanism and functional implications of this novel RNA-RNA interaction.

Main Methods:

• Bioinformatic analysis to identify potential RNA-RNA interaction sites.
• Biochemical assays to confirm binding between tRNA(Asp) and the Alu RNA element.
• RNA structure probing and analysis to understand the structural basis of the interaction.
• Reporter assays to assess the impact on mRNA polyadenylation and stability.

Main Results:

• A human tRNA(Asp) isodecoder directly binds to an embedded Alu RNA element in the 3' UTR of aspartyl-tRNA synthetase mRNA.
• This interaction is mediated by an unexpected structural motif, causing a global rearrangement of the 3' UTR.
• The 3' UTR contains two functional polyadenylation signals, and the tRNA/Alu interaction modulates their accessibility.
• The interaction regulates mRNA stability and links gene expression to RNA polymerase III transcription.

Conclusions:

• A novel regulatory mechanism involving tRNA and Alu RNA interaction controls mRNA stability and gene expression.
• This RNA-mediated regulation may be crucial for primate-specific biological pathways.
• The findings highlight a new layer of post-transcriptional gene regulation involving noncoding RNAs.