Open AccessRCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases
Author(s) -
Aurelio Reyes,
Paola Favia,
Sara Vidoni,
Vittoria Petruzzella,
Massimo Zeviani
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008923
Subject(s) - biology , mitochondrial ribosome , microbiology and biotechnology , mitochondrion , gtpase , ribosomal protein , gene isoform , ribosome , translation (biology) , genetics , rna , messenger rna , gene
Mitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to interact with the mitochondrial large ribosomal subunit. In humans, three different RCC1L isoforms have been identified that originate from alternative splicing but share the same N-terminus, RCC1L V1 , RCC1L V2 and RCC1L V3 . All three isoforms were exclusively localized to mitochondria, interacted with its inner membrane and could associate with homopolymeric oligos to different extent. Mitochondrial immunoprecipitation experiments showed that RCC1L V1 and RCC1L V3 associated with the mitochondrial large and small ribosomal subunit, respectively, while no significant association was observed for RCC1L V2 . Overexpression and silencing of RCC1L V1 or RCC1L V3 led to mitoribosome biogenesis defects that resulted in decreased translation. Indeed, significant changes in steady-state levels and distribution on isokinetic sucrose gradients were detected not only for mitoribosome proteins but also for GTPases, (GTPBP10, ERAL1 and C4orf14), and pseudouridylation proteins, (TRUB2, RPUSD3 and RPUSD4). All in all, our data suggest that RCC1L is essential for mitochondrial function and that the coordination of at least two isoforms is essential for proper ribosomal assembly.