@article{fdi:010044331,
  title = {{A}nalysis of natural variants of the hepatitis {C} virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation},
  author = {{B}arria, {M}aria {I}n{\'e}s and {G}onzalez, {A}. and {V}era {O}tarola, {J}orge and {L}eon, {U}rsula and {V}ollrath, {V}aleska and {M}arsac, {D}elphine and {M}onasterio, {O}. and {P}{\'e}rez {A}cle, {T}. and {S}oza, {A}lejandro and {L}opez {L}astra, {M}arcelo},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he {HCV} internal ribosome entry site ({IRES}) spans a region of similar to 340 nt that encompasses most of the 5' untranslated region (5'{UTR}) of the viral m{RNA} and the first 24-40 nt of the core-coding region. {T}o investigate the implication of altering the primary sequence of the 5'{UTR} on {IRES} activity, naturally occurring variants of the 5'{UTR} were isolated from clinical samples and analyzed. {T}he impact of the identified mutations on translation was evaluated in the context of {RL}uc/{FL}uc bicistronic {RNA}s. {R}esults show that depending on their location within the {RNA} structure, these naturally occurring mutations cause a range of effects on {IRES} activity. {H}owever, mutations within subdomain {III}d hinder {HCV} {IRES}-mediated translation. {I}n an attempt to explain these data, the dynamic behavior of the subdomain {III}d was analyzed by means of molecular dynamics ({MD}) simulations. {D}espite the loss of function, {MD} simulations predicted that mutant {G}266{A}/{G}268{U} possesses a structure similar to the wt-{RNA}. {T}his prediction was validated by analyzing the secondary structure of the isolated {III}d {RNA}s by circular dichroism spectroscopy in the presence or absence of {M}g2+ ions. {T}hese data strongly suggest that the primary sequence of subdomain {III}d plays a key role in {HCV} {IRES}-mediated translation.},
  keywords = {},
  booktitle = {},
  journal = {{N}ucleic {A}cids {R}esearch},
  volume = {37},
  numero = {3},
  pages = {957--971},
  ISSN = {0305-1048},
  year = {2009},
  DOI = {10.1093/nar/gkn1022},
  URL = {https://www.documentation.ird.fr/hor/fdi:010044331},
}