TY - JOUR
T1 - A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei
AU - Rajan, K. Shanmugha
AU - Madmoni, Hava
AU - Bashan, Anat
AU - Taoka, Masato
AU - Aryal, Saurav
AU - Nobe, Yuko
AU - Doniger, Tirza
AU - Galili Kostin, Beathrice
AU - Blumberg, Amit
AU - Cohen-Chalamish, Smadar
AU - Schwartz, Schraga
AU - Rivalta, Andre
AU - Zimmerman, Ella
AU - Unger, Ron
AU - Isobe, Toshiaki
AU - Yonath, Ada
AU - Michaeli, Shulamit
PY - 2023/12
Y1 - 2023/12
N2 - Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal. A single knock-out of a snoRNA guiding Ψ530 on H69 altered the composition of the 80S monosome. These changes specifically affected the translation of only a subset of proteins. This study correlates a single site Ψ modification with changes in ribosomal protein stoichiometry, supported by a high-resolution cryo-EM structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.
AB - Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal. A single knock-out of a snoRNA guiding Ψ530 on H69 altered the composition of the 80S monosome. These changes specifically affected the translation of only a subset of proteins. This study correlates a single site Ψ modification with changes in ribosomal protein stoichiometry, supported by a high-resolution cryo-EM structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.
UR - http://www.scopus.com/inward/record.url?scp=85177196963&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-43263-6
DO - 10.1038/s41467-023-43263-6
M3 - Article
C2 - 37985661
AN - SCOPUS:85177196963
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7462
ER -