Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: the IRES functions as an RNA-based translation factor.
Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-like IRES elements seem to act as RNA-based translation factors.
Spahn
Christian M T
CM
Howard Hughes Medical Institute, Health Research Inc. at, Albany, NY 10012, USA.
Jan
Eric
E
Mulder
Anke
A
Grassucci
Robert A
RA
Sarnow
Peter
P
Frank
Joachim
J
D017124:Conserved Sequence; D020285:Cryoelectron Microscopy / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*
D012333:RNA, Messenger; D012367:RNA, Viral; D012343:RNA, Transfer