Internal translation initiation from HIV-1 transcripts is conferred by a common RNA structure

Area of Science:

• Molecular Biology
• Virology
• RNA Biology

Background:

• Alternative splicing of human immunodeficiency virus 1 (HIV-1) RNA generates transcripts for nine viral proteins.
• Each transcript leader contains a common non-coding exon at the 5' end.
• Previous studies indicated that some HIV-1 leaders function as internal ribosome entry sites (IRESs) for protein synthesis.

Purpose of the Study:

• To determine if the common exon acts as a universal IRES element or if distinct IRESs exist in each HIV-1 leader.
• To investigate the relationship between IRES activity and initiation codon selection in HIV-1 transcripts.

Main Methods:

• Comparative analysis of 5' leader sequences and structures across different HIV-1 transcripts.
• Functional assays to assess IRES activity and protein synthesis initiation.
• Investigation of ribosome scanning mechanisms and start codon identification.

Main Results:

• The common exon maintains a similar conformation across all studied HIV-1 leaders.
• Sequence and structure of the common exon are essential for IRES activity.
• All analyzed HIV-1 leaders utilize a scanning mechanism for initiation codon identification.

Conclusions:

• The common exon of HIV-1 transcripts functions as a conserved IRES element, acting as a ribosome landing site.
• This mechanism involves recruiting preinitiation complexes upstream of the initiation codon, followed by scanning to the AUG.
• This model explains how HIV-1 achieves protein synthesis from alternatively spliced transcripts.