Exploration of essential gene functions via titratable promoter alleles

Sanie Mnaimneh; Armaity P. Davierwala; Jennifer Haynes; Jason Moffat; Wen Tao Peng; Wen Zhang; Xueqi Yang; Jeff Pootoolal; Gordon Chua; Andres Lopez; Miles Trochesset; Darcy Morse; Nevan J. Krogan; Shawna L. Hiley; Zhijian Li; Quaid Morris; Jörg Grigull; Nicholas Mitsakakis; Christopher J. Roberts; Jack F. Greenblatt; Charles Boone; Chris A. Kaiser; Brenda J. Andrews; Timothy R. Hughes

doi:10.1016/j.cell.2004.06.013

Exploration of essential gene functions via titratable promoter alleles

Sanie Mnaimneh, Armaity P. Davierwala, Jennifer Haynes, Jason Moffat, Wen Tao Peng, Wen Zhang, Xueqi Yang, Jeff Pootoolal, Gordon Chua, Andres Lopez, Miles Trochesset, Darcy Morse, Nevan J. Krogan, Shawna L. Hiley, Zhijian Li, Quaid Morris, Jörg Grigull, Nicholas Mitsakakis, Christopher J. Roberts, Jack F. GreenblattCharles Boone, Chris A. Kaiser, Brenda J. Andrews, Timothy R. Hughes

Research output: Contribution to journal › Article › peer-review

501 Scopus citations

Abstract

Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.

Original language	English
Pages (from-to)	31-44
Number of pages	14
Journal	Cell
Volume	118
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2004.06.013
State	Published - 9 Jul 2004
Externally published	Yes

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Mnaimneh, S., Davierwala, A. P., Haynes, J., Moffat, J., Peng, W. T., Zhang, W., Yang, X., Pootoolal, J., Chua, G., Lopez, A., Trochesset, M., Morse, D., Krogan, N. J., Hiley, S. L., Li, Z., Morris, Q., Grigull, J., Mitsakakis, N., Roberts, C. J., ... Hughes, T. R. (2004). Exploration of essential gene functions via titratable promoter alleles. Cell, 118(1), 31-44. https://doi.org/10.1016/j.cell.2004.06.013

@article{8fd658cc3dfb42b8822e02076249fe58,

title = "Exploration of essential gene functions via titratable promoter alleles",

abstract = "Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.",

author = "Sanie Mnaimneh and Davierwala, {Armaity P.} and Jennifer Haynes and Jason Moffat and Peng, {Wen Tao} and Wen Zhang and Xueqi Yang and Jeff Pootoolal and Gordon Chua and Andres Lopez and Miles Trochesset and Darcy Morse and Krogan, {Nevan J.} and Hiley, {Shawna L.} and Zhijian Li and Quaid Morris and J{\"o}rg Grigull and Nicholas Mitsakakis and Roberts, {Christopher J.} and Greenblatt, {Jack F.} and Charles Boone and Kaiser, {Chris A.} and Andrews, {Brenda J.} and Hughes, {Timothy R.}",

note = "Funding Information: We thank HuiMing Ding, Amy Tong, Renee Brost, Diana Ho, Nina Enriques, Darlene Ellenor, Mariana Kekis, Natalie Gabovic, Melissa Ballantine, and Jialin Wu for technical contributions; Dawn Richards and Victoria Canadien for assistance with mass spectrometry; Michael Yaffe, Howard Bussey, Roberto J. Rodriguez-Suarez, and Arnis Kuksis for advice and assistance in analyzing specific strains; and Grant Brown for evaluation of the manuscript. This work was supported by grants from the CIHR and Genome Canada to T.R.H. and B.J.A. A.D. was supported by a Charles H. Best fellowship and J.H. was supported by an Estate of Betty Irene West/CIHR doctoral research award. ",

year = "2004",

month = jul,

day = "9",

doi = "10.1016/j.cell.2004.06.013",

language = "English",

volume = "118",

pages = "31--44",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "1",

}

Mnaimneh, S, Davierwala, AP, Haynes, J, Moffat, J, Peng, WT, Zhang, W, Yang, X, Pootoolal, J, Chua, G, Lopez, A, Trochesset, M, Morse, D, Krogan, NJ, Hiley, SL, Li, Z, Morris, Q, Grigull, J, Mitsakakis, N, Roberts, CJ, Greenblatt, JF, Boone, C, Kaiser, CA, Andrews, BJ & Hughes, TR 2004, 'Exploration of essential gene functions via titratable promoter alleles', Cell, vol. 118, no. 1, pp. 31-44. https://doi.org/10.1016/j.cell.2004.06.013

TY - JOUR

T1 - Exploration of essential gene functions via titratable promoter alleles

AU - Mnaimneh, Sanie

AU - Davierwala, Armaity P.

AU - Haynes, Jennifer

AU - Moffat, Jason

AU - Peng, Wen Tao

AU - Zhang, Wen

AU - Yang, Xueqi

AU - Pootoolal, Jeff

AU - Chua, Gordon

AU - Lopez, Andres

AU - Trochesset, Miles

AU - Morse, Darcy

AU - Krogan, Nevan J.

AU - Hiley, Shawna L.

AU - Li, Zhijian

AU - Morris, Quaid

AU - Grigull, Jörg

AU - Mitsakakis, Nicholas

AU - Roberts, Christopher J.

AU - Greenblatt, Jack F.

AU - Boone, Charles

AU - Kaiser, Chris A.

AU - Andrews, Brenda J.

AU - Hughes, Timothy R.

N1 - Funding Information: We thank HuiMing Ding, Amy Tong, Renee Brost, Diana Ho, Nina Enriques, Darlene Ellenor, Mariana Kekis, Natalie Gabovic, Melissa Ballantine, and Jialin Wu for technical contributions; Dawn Richards and Victoria Canadien for assistance with mass spectrometry; Michael Yaffe, Howard Bussey, Roberto J. Rodriguez-Suarez, and Arnis Kuksis for advice and assistance in analyzing specific strains; and Grant Brown for evaluation of the manuscript. This work was supported by grants from the CIHR and Genome Canada to T.R.H. and B.J.A. A.D. was supported by a Charles H. Best fellowship and J.H. was supported by an Estate of Betty Irene West/CIHR doctoral research award.

PY - 2004/7/9

Y1 - 2004/7/9

N2 - Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.

AB - Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.

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U2 - 10.1016/j.cell.2004.06.013

DO - 10.1016/j.cell.2004.06.013

M3 - Article

C2 - 15242642

AN - SCOPUS:3142536716

SN - 0092-8674

VL - 118

SP - 31

EP - 44

JO - Cell

JF - Cell

IS - 1

ER -

Exploration of essential gene functions via titratable promoter alleles

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