Revealing the density of encoded functions in a viral RNA

TY - JOUR

T1 - Revealing the density of encoded functions in a viral RNA

AU - Patel, Nikesh

AU - Dykeman, Eric C.

AU - Coutts, Robert H. A.

AU - Lomonossoff, George P.

AU - Rowlands, David J.

AU - Phillips, Simon E. V.

AU - Ranson, Neil

AU - Twarock, Reidun

AU - Tuma, Roman

AU - Stockley, Peter G.

A2 - Johnson, John E.

PY - 2015/2/17

Y1 - 2015/2/17

N2 - We present direct experimental evidence that assembly of a single-stranded RNA virus occurs via a packaging signal-mediated mechanism. We show that the sequences of coat protein recognition motifs within multiple, dispersed, putative RNA packaging signals, as well as their relative spacing within a genomic fragment, act collectively to influence the fidelity and yield of capsid selfassembly in vitro. These experiments confirm that the selective advantages for viral yield and encapsidation specificity, predicted from previous modeling of packaging signal-mediated assembly, are found in Nature. Regions of the genome that act as packaging signals also function in translational and transcriptional enhancement, as well as directly coding for the coat protein, highlighting the density of encoded functions within the viral RNA. Assembly and gene expression are therefore direct molecular competitors for different functional folds of the same RNA sequence. The strongest packaging signal in the test fragment, encodes a region of the coat protein that undergoes a conformational change upon contact with packaging signals. A similar phenomenon occurs in other RNA viruses for which packaging signals are known. These contacts hint at an even deeper density of encoded functions in viral RNA, which if confirmed, would have profound consequences for the evolution of this class of pathogens.

AB - We present direct experimental evidence that assembly of a single-stranded RNA virus occurs via a packaging signal-mediated mechanism. We show that the sequences of coat protein recognition motifs within multiple, dispersed, putative RNA packaging signals, as well as their relative spacing within a genomic fragment, act collectively to influence the fidelity and yield of capsid selfassembly in vitro. These experiments confirm that the selective advantages for viral yield and encapsidation specificity, predicted from previous modeling of packaging signal-mediated assembly, are found in Nature. Regions of the genome that act as packaging signals also function in translational and transcriptional enhancement, as well as directly coding for the coat protein, highlighting the density of encoded functions within the viral RNA. Assembly and gene expression are therefore direct molecular competitors for different functional folds of the same RNA sequence. The strongest packaging signal in the test fragment, encodes a region of the coat protein that undergoes a conformational change upon contact with packaging signals. A similar phenomenon occurs in other RNA viruses for which packaging signals are known. These contacts hint at an even deeper density of encoded functions in viral RNA, which if confirmed, would have profound consequences for the evolution of this class of pathogens.

KW - Packaging signal

KW - Satellite tobacco necrosis virus

KW - Single-molecule fluorescence correlation spectroscopy

KW - Virus assembly

UR - http://www.scopus.com/inward/record.url?scp=84923271402&partnerID=8YFLogxK

U2 - 10.1073/pnas.1420812112

DO - 10.1073/pnas.1420812112

M3 - Article

AN - SCOPUS:84923271402

SN - 0027-8424

VL - 112

SP - 2227

EP - 2232

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 7

ER -