Wirusy mistrzami mimikry

Mimo że wirusów nie można jednoznacznie określić jako żywe ze względu na prostą strukturę, to sprytnych rozwiązań funkcjonalnych mógłby im pozazdrościć niejeden organizm. Wirusy nie potrafią samodzielnie się rozmnażać, ale wykorzystują do tego maszynerię komórkową gospodarza, stosując najróżniejsze strategie. Wirusy RNA, których materiał genetyczny służy bezpośrednio jako matryca do syntezy białek w komórkach eukariotycznych, znalazły wiele sposobów na efektywne włączenie się w proces translacji gospodarza.

Przykładem takiego pasożyta komórkowego jest wirus żółtej mozaiki rzepy TYMV (ang. Turnip Yellow Mosaic Virus). Podobnie jak u wielu wirusów tego typu na 3’ końcu jego genomowego RNA nie ma ogona poly(A) – elementu strukturalnego charakterystycznego dla eukariotycznego mRNA i ważnego z punktu widzenia promowania translacji – i, podobnie jak u tych wirusów, w obrębie regionu 3’ UTR występuje inny element strukturalny, który pełni rolę „wzmacniacza” (ang. enhancer) translacji. W przypadku wirusa TYMV ten element to 82-nukleotydowy fragment łańcucha RNA, który strukturalnie przypomina tRNA, stąd jego nazwa: struktura TLS (ang. tRNA-like structure). Struktura TLS bierze udział w promowaniu translacji, działając razem ze znajdującym się tuż przed nią nieco ponad dwudziestonukleotydowym fragmentem UPSK (ang. upstream pseudoknot) oraz 5’ capem. W obrębie tej struktury, tak samo jak we właściwym tRNA, może zachodzić aminoacylacja, która prowadzi do uzyskania wirusowego aminoacylo-RNA. Jeśli dołączona w ten sposób zostanie walina, to znacznemu wzmocnieniu ulega powinowactwo do czynnika elongacji translacji eEF1A∙GTP, co skutkuje efektywniejszą inicjacją syntezy białka. Z drugiej strony wiązanie eEF1A∙GTP z materiałem genetycznym wirusa powoduje inhibicję procesu amplifikacji genomu wirusowego przez RNA-zależną RNA polimerazę. Najprawdopodobniej represja ta ma miejsce w początkowych fazach infekcji, kiedy istotna jest koordynacja dwóch konkurujących procesów – translacji i replikacji RNA. W czerwcu tego roku w Nature ukazał się artykuł, w którym przedstawiono strukturę krystalograficzną TLS. Bardzo dobra rozdzielczość pozwoliła na dostrzeżenie kilku ciekawych faktów. Okazało się, że globalnie podobna do tRNA struktura TLS istnieje dzięki zupełnie innym oddziaływaniom międzycząsteczkowym pozwalającym uzyskać kształt cząsteczki transportowego RNA. Te oddziaływania ułatwiają również sprawne przejścia do innej konformacji. Ponadto naukowcy ustalili, że struktura TLS ma „dwie twarze” – jedna z dwóch wyodrębnionych części całkowicie upodabnia się do tRNA i jest odpowiedzialna za proces aminoacylacji, zaś druga znacząco różni się od tRNA i związana jest z dodatkowymi funkcjami. W tej samej pracy naukowcy przedstawili specyficzne wiązanie struktury TLS z rybosomem.

Wirus TYMV i jego struktura TLS to tylko jeden z licznych przykładów na to, jak bardzo ewolucja zadbała o „prymitywne” twory natury, jakimi są wirusy, które teraz dzięki temu mogą cieszyć się tytułem mistrzów pasożytnictwa komórkowego.

TLS

Źródła:

  1. Timothy M. Colussi, David A. Costantino, John A. Hammond, Grant M. Ruehle,  Jay C. Nix & Jeffrey S. Kieft, The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA, Nature 511 (2014), 366–369.
  2. Daiki Matsuda, Shigeo Yoshinari, and Theo W. Drehera, eEF1A binding to aminoacylated viral RNA represses minus strand synthesis by TYMV RNA-dependent RNA polymerase, Virology 321 (2004) 47– 56.
  3. Daiki Matsuda and Theo W. Drehera, The tRNA-like structure of Turnip yellow mosaic virus RNA is a 3V-translational enhancer, Virology 321 (2004) 36–46.

 

 

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