The RNA Pirate Republic

Group leader
Israel S. Fernández

Biofisika Institute (CSIC-UPV/EHU)
Science Park of the UPV/EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)

Research goal

RNA molecules are present in key molecular processes across all kingdoms of life, often playing essential regulatory roles. The ancient origin of RNA, predating cellular life itself, probably explain their pervasive role in biology. Often, RNA molecules are involved in molecular conflicts, like hostile takeovers of cellular components or weaponized as part of nucleic acid targeting complexes.

However ubiquitous, mechanistic understanding of RNA molecules, especially structural knowledge, remains scarce. We intent to explore aspects of RNA biology as molecular pirates, focusing on how viruses use RNA molecules to hijack cellular ribosomes to gain access to the cellular machinery for protein production. These RNA molecules, termed Internal Ribosomal Entry Sites or IRES, are common in viruses with single stranded RNA in the positive sense as genetic material or (+)-ssRNA viruses. We rely on electron imaging techniques, especially single particle electron-cryo microscopy (CryoEM) to structurally characterize IRES sequences in its ribosome bound state.

Thousands of new (+)-ssRNA viruses were discovered by metagenomic approaches, revealing a vast landscape of uncharacterized IRES sequences. We believe there is exciting biology hidden in the RNA Pirate Republic of IRESs.


Group members
Ikerbasque Research Professor
Postdoctoral Fellow
Research Technician

Read the article

Hoffmann FT, Kim M, Beh LY, Wang J, Vo PLH, Gelsinger DR, George JT, Acree C, Mohabir JT, Fernández IS, Sternberg SH.

Selective TnsC recruitment enhances the fidelity of RNA-guided transposition
Nature. 2022 Sep;609(7926):384-393
doi: 10.1038/s41586-022-05059-4

Read the article

Lapointe CP, Grosely R, Sokabe M, Alvarado C, Wang J, Montabana E, Villa N, Shin BS, Dever TE, Fraser CS, Fernández IS, Puglisi JD.

eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining
Nature. 2022 Jul;607(7917):185-190
doi: 10.1038/s41586-022-04858-z

Read the article

Neupane R, Pisareva VP, Rodriguez CF, Pisarev AV, Fernández IS
A complex IRES at the 5'-UTR of a viral mRNA assembles a functional 48S complex via an uAUG intermediate
Elife. 2020 Apr 14;9:e54575.
doi: 10.7554/eLife.54575

Read the article

Pisareva VP, Pisarev AV, Fernández IS
Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
Elife. 2018 Jun 1;7:e34062
doi: 10.7554/eLife.34062

Read the article

Fernández IS, Bai XC, Murshudov G, Scheres SH, Ramakrishnan V
Initiation of translation by cricket paralysis virus IRES requires its translocation in the ribosome
Cell. 2014 May 8;157(4):823-31
doi: 10.1016/j.cell.2014.04.015