Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae.

Abstract:

:The Saccharomyces cerevisiae kinase/adenosine triphosphatase Rio1 regulates rDNA transcription and segregation, pre-rRNA processing and small ribosomal subunit maturation. Other roles are unknown. When overexpressed, human ortholog RIOK1 drives tumor growth and metastasis. Likewise, RIOK1 promotes 40S ribosomal subunit biogenesis and has not been characterized globally. We show that Rio1 manages directly and via a series of regulators, an essential signaling network at the protein, chromatin and RNA levels. Rio1 orchestrates growth and division depending on resource availability, in parallel to the nutrient-activated Tor1 kinase. To define the Rio1 network, we identified its physical interactors, profiled its target genes/transcripts, mapped its chromatin-binding sites and integrated our data with yeast's protein-protein and protein-DNA interaction catalogs using network computation. We experimentally confirmed network components and localized Rio1 also to mitochondria and vacuoles. Via its network, Rio1 commands protein synthesis (ribosomal gene expression, assembly and activity) and turnover (26S proteasome expression), and impinges on metabolic, energy-production and cell-cycle programs. We find that Rio1 activity is conserved to humans and propose that pathological RIOK1 may fuel promiscuous transcription, ribosome production, chromosomal instability, unrestrained metabolism and proliferation; established contributors to cancer. Our study will advance the understanding of numerous processes, here revealed to depend on Rio1 activity.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Iacovella MG,Bremang M,Basha O,Giacò L,Carotenuto W,Golfieri C,Szakal B,Dal Maschio M,Infantino V,Beznoussenko GV,Joseph CR,Visintin C,Mironov AA,Visintin R,Branzei D,Ferreira-Cerca S,Yeger-Lotem E,De Wulf P

doi

10.1093/nar/gky618

subject

Has Abstract

pub_date

2018-09-06 00:00:00

pages

7586-7611

issue

15

eissn

0305-1048

issn

1362-4962

pii

5054092

journal_volume

46

pub_type

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