Host function of MAK16: G1 arrest by a mak16 mutant of Saccharomyces cerevisiae.

Wickner, Reed B.

doi:10.1073/pnas.85.16.6007

Cited by 31 publications

(21 citation statements)

References 43 publications

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“…Surprisingly, 18 mak mutants (mak1, mak2, mak5, mak6, mak7, mak8, mak9, mak11, mak12, mak13, mak14, mak16, mak17, mak20, mak22, mak23, mak24, and mak27 mutants) have decreased free 60S subunits like the mak7 disruptant. CEN plasmids carrying MAK1, MAK7, MAK11, or MAK16 (22,43,51) introduced into the respective mutants restored the level of free 60S subunits to a normal level, showing that it was, in fact, the mak mutation in these strains that produced the 60S subunit deficiency (Fig. 6).…”

Section: Resultsmentioning

confidence: 99%

“…MAK3 encodes an N-acetyltransferase whose acetylation of the N terminus of Gag is required by L-A and M 1 for viral assembly (39)(40)(41). MAK1 (TOP1) encodes DNA topoisomerase I (44), MAK8 (TCM1) encodes ribosomal protein L3 (55), MAK11 encodes an essential membrane-associated protein with ␤-transducin repeats (22), and MAK16 is an essential gene encoding a nuclear protein whose temperature-sensitive mutant arrests in G 1 (51). Some GCD1, GCD10, GCD11, and GCD13 mutants also have a Mak Ϫ phenotype (19).…”

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Yeast Virus Propagation Depends Critically on Free 60S Ribosomal Subunit Concentration

Ohtake

Wickner

1995

Molecular and Cellular Biology

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Over 30 MAK (maintenance of killer) genes are necessary for propagation of the killer toxin-encoding M 1 satellite double-stranded RNA of the L-A virus. Sequence analysis revealed that MAK7 is RPL4A, one of the two genes encoding ribosomal protein L4 of the 60S subunit. We further found that mutants with mutations in 18 MAK genes (including mak1 [top1], mak7 [rpl4A], mak8 [rpl3], mak11, and mak16) had decreased free 60S subunits. Mutants with another three mak mutations had half-mer polysomes, indicative of poor association of 60S and 40S subunits. The rest of the mak mutants, including the mak3 (N-acetyltransferase) mutant, showed a normal profile. The free 60S subunits, L-A copy number, and the amount of L-A coat protein in the mak1, mak7, mak11, and mak16 mutants were raised to the normal level by the respective normal single-copy gene. Our data suggest that most mak mutations affect M 1 propagation by their effects on the supply of proteins from the L-A virus and that the translation of the non-poly(A) L-A mRNA depends critically on the amount of free 60S ribosomal subunits, probably because 60S association with the 40S subunit waiting at the initiator AUG is facilitated by the 3 poly(A).Studies of viral propagation generally concentrate on the activities and interactions of virus-encoded proteins. However, the host environment and particular host components can play a crucial role in whether viral propagation is persistent or causes pathology to the host. This is amply demonstrated by studies of the roles of cellular components in bacteriophage replication and assembly.Studies of the L-A double-stranded RNA (dsRNA) virus and its killer toxin-encoding satellite, M 1 dsRNA, have identified many genes of its host, Saccharomyces cerevisiae, which either repress viral propagation (the SKI genes, so named for the superkiller phenotype of mutants in these genes) or are necessary for M 1 propagation (MAK genes, for maintenance of killer). Recently, the SKI2, SKI3, and SKI8 genes have been shown to act by specifically repressing the translation of nonpoly(A) mRNAs, such as the L-A and M 1 mRNAs (28a). In this report, we examine the mechanism by which most of the MAK genes promote viral propagation.The L-A dsRNA virus of S. cerevisiae has two open reading frames in its positive strand, the 5Ј gag encoding its major coat protein (Gag) and the 3Ј pol encoding the multifunctional Pol domain of the Gag-Pol fusion protein. M 1 is a dsRNA satellite of L-A, depending on the L-A-encoded Gag and Gag-Pol for its propagation. M 1 itself encodes no proteins required for its propagation but does encode the killer toxin, a secreted heterodimer protein processed out of a 32-kDa preprotoxin. The L-A genome lacks both 5Ј cap and 3Ј poly(A) (10, 42), and viral transcripts made in vitro lack both modifications, although a single uncoded A (or G) residue is found at the 3Ј end of both viral strands (11,42).Mutants isolated by their inability to propagate the M 1 dsRNA identify about 30 chromosomal MAK genes. MAK3 encodes an N-acetyltran...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Yeast Virus Propagation Depends Critically on Free 60S Ribosomal Subunit Concentration

Ohtake

Wickner

1995

Molecular and Cellular Biology

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106

124

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“…The mapped segment (Fig. 1) extended from 3 kb to the left of MAK16 to SPO7 and encoded 16 vegetatively expressed polyadenylated transcripts, including those of the previously characterized genes AL4K16 (63,64), LTEI (64), CCR4 (36), FUN30 (4), FUN31 (5), TPD3 (60), DEPI (31), and CYS3 (3,44). The locations and sizes of the known transcripts were consistent with the previous studies, except for the MAKJ6 and LTEI transcript sizes, which were substantially different (see Discussion).…”

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confidence: 99%

“…The transcription map of a 42-kb region is described. 4[he nucleotide sequence of most of this region has been determined (45,63,64 (52).…”

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Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: analysis of the genes in the FUN38-MAK16-SPO7 region

Barton

Kaback

1994

J Bacteriol

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Transcribed regions on a 42-kb segment of chromosome I from Saccharomyces cerevisiae were mapped.Polyadenylated transcripts corresponding to eight previously characterized genes (AL4K16, LTE1, CCR4, FUN30, FUN31, TPD3, DEPI, and CYS3) and eight new genes were identified. All transcripts were present at one to four copies per cell except for one which was significantly less abundant. This region has been sequenced, and the sizes, locations, and orientations of the transcripts were in nearly perfect agreement with the open reading frames. Disruptions in eight genes identified solely on the basis of a transcribed region, FUN38, FUN25, FUN26, FUN28, FUN30, FUN31, FUN33, and FUN34, indicated that all were nonessential for growth on rich medium at 30°C. Disruption of FUN30, a gene closely related to RAD16 and RAD54, surprisingly resulted in increased resistance to UV irradiation. No additional phenotypes, other than slow growth, were observed for all other mutants. The distribution of essential genes on chromosome I is discussed.

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“…These gene products include two ribosomal proteins (MAK7, MAK8 [24,45]), an N-acetyltransferase (MAK3 [35]), DNA topoisomerase I (MAK1 [36]), a membrane-associated protein that has homology with Cdc4p and ␤-transducin (MAK11 [15]), a nuclear protein required to transit G 1 (MAK16 [41]), and a protein needed for optimal growth on nonfermentable carbon sources with local similarities to the ␣ subunits of T-cell receptors (MAK10 [19]). While the individual properties of many of the MAK genes have been identified, except for MAK3, how these proteins contribute to the maintenance of M 1 was not understood.…”

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Translation and M1 double-stranded RNA propagation: MAK18 = RPL41B and cycloheximide curing

Carroll

Wickner

1995

J Bacteriol

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MAK18 is one of nearly 30 chromosomal genes of Saccharomyces cerevisiae necessary for propagation of the killer toxin-encoding M 1 double-stranded RNA satellite of the L-A double-stranded RNA virus. We have cloned and sequenced MAK18 and find that it is identical to RPL41B, one of the two genes encoding large ribosomal subunit protein L41. The mak18-1 mutant is deficient in 60S subunits, which we suggest results in a preferential decrease in translation of viral poly(A)-deficient mRNA. We have reexamined the curing of M 1 by low concentrations of cycloheximide (G. R. Fink and C. A. Styles, Proc. Natl. Acad. Sci. USA 69:2846-2849, 1972), which is known to act on ribosomal large subunit protein L29. We find that when M 1 is supported by L-A proteins made from the poly(A)؉ mRNA of a cDNA clone of L-A, cycloheximide does not decrease the M 1 copy number, consistent with our hypothesis.Saccharomyces cerevisiae is host to several double-stranded RNA (dsRNA) viruses (reviewed in references 42 and 43). Among them is the L-A virus and its satellite M 1 , a 1.8-kb dsRNA species encapsidated in and replicated by the proteins encoded by L-A's single 4.6-kb dsRNA segment. The viral particles of L-A and M 1 are located in the cytoplasm of the yeast host. L-A and M 1 are very similar to the core particles of dsRNA viruses of higher eukaryotes, reoviruses and rotaviruses, in having replicase and transcriptase activities in the particle and perhaps in their structural symmetry (5).As for the Reoviridae, replication of L-A and M 1 is conservative, with parental strands remaining associated, and sequential, with plus (i.e., coding) and minus strands synthesized at different points of the replication cycle. Viral plus strands are synthesized in the viral particle during a transcription step which uses the minus strand of the parent genome as a template. Newly synthesized plus strands are extruded into the cytoplasm, where they are translated and then encapsidated by viral proteins to form new virus particles. Minus-strand synthesis occurs inside the viral particle during a replication step, and mature viral particles result.The L-A plus strand has two open reading frames (ORFs): ORF1 and ORF2 (16). ORF1 encodes the 76-kDa major coat protein, Gag. A combination of ORF1 and the overlapping ORF2 encodes the 180-kDa Gag-Pol fusion protein formed by a Ϫ1 ribosomal frameshift event (8,14,16). The Pol portion of this fusion protein is involved in the transcription and replication steps of the L-A and M 1 life cycles. The M 1 virus does not encode any proteins needed for its own propagation; however, it does encode a secreted protein toxin and immunity to that toxin (reviewed in reference 4). M 1 is dependent upon the protein products of L-A for its propagation (3, 44).In addition to these two L-A-encoded proteins, propagation of L-A and M 1 is affected by an assortment of chromosomal genes. These genes are divided into two groups: the SKI genes and the MAK genes. The SKI genes repress the copy number of L-A and M 1 and the translation of ...

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Host function of MAK16: G1 arrest by a mak16 mutant of Saccharomyces cerevisiae.

Cited by 31 publications

References 43 publications

Yeast Virus Propagation Depends Critically on Free 60S Ribosomal Subunit Concentration

Yeast Virus Propagation Depends Critically on Free 60S Ribosomal Subunit Concentration

Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: analysis of the genes in the FUN38-MAK16-SPO7 region

Translation and M1 double-stranded RNA propagation: MAK18 = RPL41B and cycloheximide curing

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