Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus

A Audhya

A Fatica

A Lebreton

A van Hoof

A. C Gavin

A. I Nesvizhskii

A. K Ramani

A. L Jones

Arlen W. Johnson

B Bradatsch

B Emery

B Hong

B Pertschy

B Rempola

B. K Pannone

C. C Adams

C. H Wade

D Kressler

D. J Combs

E Hurt

E Thomson

E. A Winzeler

E. M Marcotte

E. P Lei

Edward M. Marcotte

Emily Moradi

F Dragon

G Giaever

H Lin

H Liu

H Santos-Rosa

H Tschochner

I Lee

I Zemp

Insuk Lee

J Bassler

J Esguerra

J Kufel

J LaCava

J Rinke

J Venema

J White

J. D Beggs

J. R Warner

K Asano

K. A Bernstein

K. L McGary

M Fromont-Racine

M Oki

M. B Eisen

M. D Robinson

M. G Walker

M. P Washburn

Michael B. Eisen

N. B Leeds

N. J Hung

N. J Krogan

N. P Crawford

Nai-Jung Hung

P Grandi

P Harnpicharnchai

P Milkereit

P. W Piper

R Bax

R Sharan

R. J Planta

R. M Seiser

S Ghaemmaghami

S Granneman

S Lebaron

S Mnaimneh

S Tharun

S. L French

S. W Stevens

T Borggrefe

T Schafer

T. A Nissan

T. C Fleischer

T. F Menne

T. I Moy

T. R Hazbun

T. V Pestova

V. R Gerbasi

W Yao

W-T Peng

W. K Huh

Z Kiss-Laszlo

Zhihua Li

English

PubMed

Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics—an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies—to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes—most with human orthologs—to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process.This work was supported by grants from the National Science Foundation (IIS-0325116, EIA-0219061), the National Institutes of Health (NIH) (GM067779, GM076536), the Welch Foundation (F1515), and a Packard Fellowship to EMM and NIH grant GM53655 to AWJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog

Li, Zhihua

Lee, Insuk

Moradi, Emily

Hung, Nai-Jung

Johnson, Arlen W.

Marcotte, Edward M.

Texas ScholarWorks

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Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

Crossref

Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require.170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics—an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies—to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated.100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add.10 % new genes—most with human orthologs

Nai-jung Hung

CiteSeerX

Rational extension of the ribosome biogenesis pathway using network-guided genetics

Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics-an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies-to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes-most with human orthologs-to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process

Arlen W Johnson

Edward M Marcotte

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PLoS Biology

Rational extension of the ribosome biogenesis pathway using network-guided genetics.

Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

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