Predicting the sizes of large RNA molecules.

Area of Science:

• Biophysics
• Structural Biology
• Virology

Background:

• Many viral genomes consist of large single-stranded (ssRNA) molecules that must be packaged into small protein shells.
• This packaging process suggests evolutionary pressure for specific spatial properties of viral RNA, such as radius of gyration (R(g)).

Purpose of the Study:

• To develop a theory explaining how RNA sequence influences the three-dimensional size of large ssRNA molecules.
• To investigate the evolutionary pressure for compact RNA structures that facilitate viral assembly.

Main Methods:

• Introduction of the (thermal) average Maximum Ladder Distance (MLD) as a measure of RNA secondary structure 'extendedness'.
• Comparison of MLD values for viral ssRNAs with randomly permuted sequences and non-viral natural ssRNAs.
• Mapping secondary structures to a linear polymer model to predict R(g) values.

Main Results:

• Viral ssRNAs packaged into capsids exhibit consistently smaller MLD values than random or non-viral sequences.
• Predicted R(g) values for viral ssRNAs are smaller than those for non-viral sequences.
• Average MLD values for large non-viral ssRNAs scale as N(0.67+/-0.01), and R(g) values scale as N(0.34).

Conclusions:

• RNA sequence significantly impacts 3D size, with evolutionary pressure favoring compact structures for viral packaging.
• The MLD metric effectively quantifies RNA structural properties relevant to viral assembly.
• The findings provide a theoretical framework for understanding RNA size dependence on sequence and its evolutionary implications.