Time shift
YaleGerstein Lab

Time-delayed


  LSM8 and DIB1
Description
Pre-mRNA splicing in yeast requires the U1, U2, U4, U5 and U6 small nuclear ribonucleoproteins (snRNPs) and splicing factors in order to form the spliceosome (Pannone, 2001). U1, U3, U4 and U5 snRNAs are transcribed by RNA polymerase II, acquire an N7-methyl-guanosine capseen in mRNAs and are then transported to the cytoplasm (Kambach 1999). In the cytoplasm, a set of seven core Sm proteins is assembled. Pre-mRNA, U1 and U2 snRNPS form the pre-spliceosome by binding to the 5 splice site and branch point of the intron (Mayes, 1999). The U4/U6.U5 snRNP (tri-snRNP) pre-assembled complex joins the mRNA splicing reaction after the pre-spliceosome is formed (Stevens 1999).

Dib1 is an integral component of the tri-snRNP (Stevens 1999). At the 5 splice site, U1 is replaced by U6, and then U4 is released from the spliceosome, and the U2, U5 and U6 snRNPs remain associated Stevens 1999). U5 aligns the two exons that will be spliced together, some rearrrangements occur with U2 and U6, and then after the splicing occurs and the spliceosome dissociates, the tri-snRNP is reformed (Stevens 1999). A complex of Lsm proteins bind to the 3 end of the U6 snRNA and are required for the stable accumulation of U6 snRNPs (Pannone, 2001). These Lsm proteins influence the efficiency of mRNA splicing by their effects on U6 snRNA-containing complexes (Mayes, 1999). Lsm8 is one of the Lsm proteins that plays a role in conformational rearrangements of the U6 snRNP in the spliceosome association-dissociation cycle involved in mRNA splicing. The Lsm proteins are thought to facilitate the formation of the U4/U6 dimer and the tri-snRNP assembly by minimizing the energy needed for conformational rearrangements. (Mayes, 1999). Our algorithm has identified a time-lag profile relationship between DIB1 and LSM8. While it is clear that they interact in the mRNA splicing mechanism of yeast, it is interesting to think about why their mRNA levels share the same profile but occur at different time points in the oligonucleotide array data..
Reference
Kambach, C., Walke, S., Young, R., Avis, J. M., delaFortelle, E., Raker, V. A., Luhrmann, R., Li, J., and Nagai, K. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 96, 375-387 (1999).

Mayes, A. E., Verdone, L., Legrain, P., and Beggs, J. D. Characterization of Sm-like proteins in yeast and their association with U6 snRNA. Embo Journal 18, 4321-4331 (1999).

Pannone, B. K., Xue, D., and Wolin, S. L. A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is a molecular chaperone for RNA polymerase III transcripts. Embo Journal 17, 7442-53 (1998).

Stevens, S. W., and Abelson, J. Purification of the yeast U4/U6.U5 small nuclear ribonucleoprotein particle and identification of its proteins. Proc Natl Acad Sci U S A 96, 7226-31 (1999).
  J0544 and ATP11
  J0544 and MRPl17
  J0544 and MRPL19
  J0544 and yd9727.11
Description
J0544 (YJL163C) is a protein of unknown function based on MIPS and YPD, about which very little is known. Therefore it was hoped that this type of analysis could shed some light on not only known interacts but could suggest possible interactions or roles of proteins with unknown functions. Analysis of the mRNA expression of this ORF with our algorithm showed that it has a profile relationship with four mitochondrial-related mRNAs (Atp11, Mrpl17, Mrpl19 and YD9727.11). Atp11 has been found in mitochondria, and is an F1-ATP synthase assembly protein (YPD). Mrpl17 and Mrpl19 are mitochondrial ribosomal proteins of the large ribosomal subunit (YPD). YD9727.11 is a probable component of mitochondrial ribosomes, has similarity to prokaryotic ribosomal protein L1 (YPD). This suggests that J0544 may be involved in mitochondrial processes, perhaps as an activator or some other type of component. Atp11, Mrpl17, Mrpl19 and YD9729.11 are all time-delayed at approximately the same time shift as compared to J0544, and in fact those four genes were ranked as having simultaneous correlations.
  ARC35 and ARP2/3
Description
The Arp2/3 complex in yeast has six subunits. Arp2 and Arp3 are highly conserved actin-related proteins, and have been localized to the cortical actin cytoskeleton. This complex is involved in endocytosis and actin cytoskeleton organization, and binds actin and profilin. Arc35 is one of the subunits of the Arp2/3 complex. Calmodulin is coded by one gene is yeast (cmd1). It is a calcuim sensor in yeast that has a fundamental role in endocytosis, and two-hybrid and coimmunoprecipitation data show that cmd1 and arc35 interact. Arc35 has been implicated as a regulator of calmodulin localization. The results suggest that the calmodulin-dependent function of the Arp2/3 complex is mediated by the Arc35 subunit, although other subunits could be required as well. Arc35p works through two genetically separatable calmodulin functions to regulate the actin and tubulin cytoskeletons Schaerer-Brodbeck (2000)

Arc35 is required in late G1 for its cell cycle function (arc35 mutants have cell division arrest as large-budded cells). Calmodulin has four cellular functions in yeast: (1) actin organization of the cytoskeleton; (2) calmodulin localization; (3) mitotic spindle assembly and elongation; (4) bud formation; and at least two functions in endocytosis. Arc35 serves as a regulator of actin cytoskeleton organization as well as regulation of aspects of microtubule function, acting through two distinct activities of calmodulin for these two functions.
  HOR2 and D0760
Description
HOR2 is a DL-glycerol phosphate phosphatase of unknown function that is induced during aerobic growth. D0760 is also a protein of unknown function induced during anaerobic growth (YPD)
  ROX1 and COX14
Description
ROX1 is a heme-dependent transcriptional repressor of hypoxic genes, and COX14 is a protein required for the assembly of cytochrome oxidase. (YPD)
  YD9727.11 and RIP1
Description
YD9727.11 is a probably mitochondrial ribosome component with similarity to prokaryotic ribosomal protein L1. RIP1 is a ubiquinol cytochrome c reductase iron-sulfur protein that helps to function as an oxidoreduction-driven active transporter that transports proteins across the mitochondrial membrane (YPD)
  J0544 and yd9727.11
Description
J0544 (YJL163C) is a protein of unknown function based on MIPS and YPD, about which very little is known. Therefore it was hoped that this type of analysis cou ld shed some light on not only known interacts but could suggest possible interactions or roles of proteins with unknown functions. Analysis of the mRNA expres sion of this ORF with our algorithm showed that it has a profile relationship with four mitochondrial-related mRNAs (Atp11, Mrpl17, Mrpl19 and YD9727.11). Atp11 has been found in mitochondria, and is an F1-ATP synthase assembly protein (YPD). Mrpl17 and Mrpl19 are mitochondrial ribosomal proteins of the large ribosom al subunit (YPD). YD9727.11 is a probable component of mitochondrial ribosomes, has similarity to prokaryotic ribosomal protein L1 (YPD). This suggests that J0544 may be involved in mitochondrial processes, perhaps as an activator or some other type of component. Atp11, Mrpl17, Mrpl19 and YD9729.11 are all time-del ayed at approximately the same time shift as compared to J0544, and in fact those four genes were ranked as having simultaneous correlations.
  ECM13 and CWP1
Description
ECM13 is thought to be involved in cell wall structure or biosynthesis. CWP1 is known to be a mannoprotein of the cell wall. (YPD)
  AGP1 and GAP1
Description
AGP1 is a broad substrate range amino acid permease that has a high affinity for asparagine and glutamine, and GAP1 is a general amino acid permease (YPD). GAP1 and AGP1 are the main aromatic amino acid transporters in catabolism (Iraqui, 1999a). Gap1 and agp1 permease mutants have impaired ARO9 transcriptional induction (Iraqui, 1999a and Iraqui 1999b).
Reference
Iraqui, I., Vissers, S., Andre, B., and Urrestarazu, A. Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae. Mol Cell Biol 19, 3360-3371 (1999a).

Iraqui, I., Vissers, S., Bernard, F., de Craene, J. O., Boles, E., Urrestarazu, A., and Andre, B. Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease. Mol Cell Biol 19, 989-1001 (1999b).

Inverted


  Put2 and Ser3 (#1)
Description
Ser3 (YER081W), D-3-Phosphoglycerate Dehydrogenase I, is involved in synthesis of serine from 3-phosphoglycerate. Serine can be formed from intermediates from both glycolysis via phosphorylated intermediates, from glycine formed from intermediates from tricarboxylic acid cycle intermediates (Ulane and Ogur 1971), and possibly from a third pathway (Melcher and Entian, 1992). Conditional auxotrophy was found in yeast strains in which growth requirements were exhibited under one set of conditions but not under other conditions, due to blockage of the primary biosynthetic pathway (Ulane and Ogur 1971). This suggests that other pathways to a given metabolite provide a possible escape from the limitations of just one pathway in case of a mutation (Ulane and Ogur 1971). The glycolytic pathway to serine formation begins with 3-phosphyglycerate and is under the regulation of amino-acid biosynthesis and serine repression (Melcher 1991).

Put2 (YHR037W), Delta-1-pyrroline-5-Carboxylate Dehydrogenase, carries out the second step in proline degradation of the conversion of proline to glutamate for use as a nitrogen source (Brandriss 1983 and Krzywicki and Brandriss, 1984). Lundgren and Ogur (1973) demonstrated proof of the conversion of proline to glutamate. They also demonstrated the inhibition of Delta-1-pyrroline-5-Carboxylate Dehydrogenase by serine (and other amino acids ) in the conversion of proline to glutamate (Lundgren and Ogur, 1973).

In both glutamate synthesis from proline degradation (via Put2) and serine biosynthesis (via Ser3), single mutations in the primary pathways produce auxotrophy due to tight regulation of secondary metabolic pathways by amino acid biosynthesis inhibition or catabolite repression (Lundgren and Ogur, 1973). Therefore, it is possible that some genetic mutations can be circumvented by the use and regulation of exisiting secondary pathways (Lundgren and Ogur, 1973). The profiles of Put2 and Ser3 show very high correlation as an inverted relationship, as shown in Figure ****. In the light of amino acid degradation and biosynthesis pathway intermediates overlapping and regulation, it is possible that they are biologically related by such pathway relationships, interactions, or control as suggested by Lundgren and Ogur (1973). Even though a direct inhibition and regulation has not been demonstrated in the literature between Put2 and Ser3, their highly correlated profiles and scientific background suggests such an inhibitory regulation mechanism exists between these two enzymes.
Reference
Lundgren, D. W., and Ogur, M. Inhibition of yeast 1 -pyrroline-5-carboxylate dehydrogenase by common amino acids and the regulation of proline catabolism. Biochim Biophys Acta 297, 246-57 (1973).

Brandriss, M. C. Proline utilization in Saccharomyces cerevisiae: analysis of the cloned PUT2 gene. Mol Cell Biol 3, 1846-56 (1983).

Krzywicki, K. A., and Brandriss, M. C. Primary structure of the nuclear PUT2 gene involved in the mitochondrial pathway for proline utilization in Saccharomyces cerevisiae. Mol Cell Biol 4, 2837-42 (1984).

Melcher, K., and Entian, K. D. Genetic analysis of serine biosynthesis and glucose repression in yeast. Curr Genet 21, 295-300 (1992).

Ulane, R. and Ogur, M. Genetic and physiological control of serine and glycine biosynthesis in Saccharomyces. J. Bacteriol. 109:34-43 (1972).
  YME1/YNT20 (#405)
Description
Yme genes were found when looking for mitochondrial DNA escape genes (DNA that escaped from the mitochondria and migrated to the nucleus). Yme1 is an ATP and metal-dependent protease associated with the inner mitochondrial membrane as part of a larger complex of proteins that are through to control the assembly and degradation of multisubunit protein complexes. Ynt20 has a mitochondrial targeting sequence, 3'-5' exonuclease motifs, a sequence element that can be cleaved in one step by the mitochondrial processing peptidase (MPP), and a motif typical for precursors cleaved in two steps by MPP and the mitochondrial intermediate peptidase (MIP). YNT20 is thereby thought to be a part of the Yme-1 mediated mitochondrial DNA escape pathway, such as by metabolism of RNA or mitochondrial DNA due to its 3'-5' exonuclease activity. [Hanekamp, 1999 #5].
  ATF1 and MSF1 (#29)
  ATF1 and MSF1 (#12)
Description
ATF1 is an alcohol acetyltransferase that catalyzes the condensation of acetyl-CoA to various alcohols to produce acetate esters (YPD). ATF1 has an inverted relationship with both MSF1 is a phenylanlanyl-tRNA synthetase, and MSY1 a tyrosyl-tRNA synthetase.(YPD)
  SER3 (YER081W) and MSF1 (#23)
Description
Ser3 (YER081W), D-3-Phosphoglycerate Dehydrogenase I, is involved in synthesis of serine from 3-phosphoglycerate. MSF1 is a phenylanlanyl-tRNA synthetase. (YPD).
GAL11 has an inverted relationship with many mitochondrial proteins (see below)
  GAL11 and MRPL10 (#51)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription. MRPL10 is a mitochondrial ribosomal protein of the large subunit, as well as a member of the L15 family of prokaryotic ribosomal proteins. (YPD)
  GAL11 and NDE1 (#1806)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription. NDE1 is Mitochondrial NADH dehydrogenase that catalyzes cytosolic NADH oxidation
  GAL11 and RPN2 (#2520)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription
  GAL11 and RPN8 (#409)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription
  GAL11 and RPT3 (#2791)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription
  GAL11 and RPT4 (#2678)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription
  GAL11 and YM9375.03 (#2922)
Description
GAL11 is a Component of RNA polymerase II holoenzyme and Kornberg's mediator complex with positive and negative effects on transcription. YM9375.03 is a mitochondrial NADH dehydrogenase that catalyzes cytosolic NADH oxidation
  AD53 and 02333 (#1014)
   RAD27 and 02333 (#1209)
Description
02333 (YOL014W) is a protein of unknown function (YPD). RAD53 is a serine/threonine/tyrosine protein kinase with a checkpoint function in S and G2 phases that acts to prevent mitosis from occurring in cells with DNA damage or with unreplicated DNA (YPD) RAD27 is a single-stranded DNA endonuclease and 5'-3' exonuclease that functions in the MSH2-MLH1-PMS1-dependent mismatch repair system. Its inverted profile relationship with RAD53 and RAD27 suggests that it could be involved in the inhibition, or is inhibited by, these DNA repair and checkpoint mechanisms.
  RAD54 and CDC20 (#1254)
Description
RAD54 is a DNA-dependent ATPase of the Snf2p family that is required for mitotic recombination and DNA repair of X-ray damage (YPD). CDC20 is required for microtubule function during mitosis and for exiting anaphase. (YPD)
N1909 (YNL120C) has an inverted relationship with many ribosomal proteins
N1909 is a protein of unknown function, is an internal ORF to TOM70
  N1909 and RPL11B
Description
Ribosomal protein L7 (yeast L6; YL8B; rp11; E. coli L30; rat L7), nearly identical to Rpl7Ap
  N1909 and RPL22A
Description
Ribosomal protein L22, similar to Rpl22Bp
  N1909 and RPL31B
Description
Ribosomal protein L31 (yeast L34; YL36; YL28; rat L31), nearly identical to Rpl31Ap
  N1909 and RPL33A
Description
Ribosomal protein L33 (yeast L37; YL37; rp47; rat L35A), nearly identical to Rpl33Bp
  N1909 and RPL33B
Description
Ribosomal protein L33 (yeast L37; YL37; rp47; rat L35A), nearly identical to Rpl33Ap
  N1909 and RPL34B
Description
Ribosomal protein L34 (rat L34), nearly identical to Rpl34Ap
  N1909 and RPL37A
Description
Ribosomal protein L37 (yeast L46; rat L37), nearly identical to Rpl37Bp
  N1909 and RPL38
Description
Ribosomal protein L38
  N1909 and RPL40B
Description
Fusion protein comprised of ribosomal protein L40 (C-terminal half) and ubiquitin (N-terminal half), (rat L40), identical to Rpl40Ap
  N1909 and RPL7B
Description
Ribosomal protein L7 (yeast L6; YL8B; rp11; E. coli L30; rat L7), nearly identical to Rpl7Ap
  N1909 and RPS1A
Description
Ribosomal protein S1 (rp10; rat S3A), nearly identical to Rps1Bp
  N1909 and RPS28A
Description
Ribosomal protein S28 (yeast S33; YS27; mammalian S28), nearly identical to Rps28Bp
  N1909 and RPS3
Description
Ribosomal protein S3 (rp13; YS3; mammalian S3), has a possible KH domain
  N1909 and RPS30B
Description
Ribosomal protein S30B (mammalian S30), identical to Rps30Ap
  N1909 and RPS31
Description
usion protein comprised of ribosomal protein S31 at the C-terminal half fused to ubiquitin at the N-terminal half (yeast S37;YS24; rat S27a)
SMK1 has an inverted relationship to many ribosomal proteins
SKM1 is a sporulation-specific protein kinase (MAP family) that is required for completion of sporulation (YPD)
  SMK1 and PDC1
Description
Pyruvate decarboxylase isozyme 1
  SMK1 and RPL10
Description
Ribosomal protein L10 (yeast L9)
  SMK1 and RPL11A
Description
Ribosomal protein L11 (yeast L16; YL22; rp39A; E. coli L5; rat L11), nearly identical to Rpl11Bp
  SMK1 and RPL22A
Description
Ribosomal protein L22, similar to Rpl22Bp
  SMK1 and RPL33B
Description
Ribosomal protein L33 (yeast L37; YL37; rp47; rat L35A), nearly identical to Rpl33Ap
  SMK1 and RPL38
Description
Ribosomal protein L38
  SMK1 and RPL7A
Description
Ribosomal protein L7 (yeast L6; YL8A; rp11; E. coli L30; rat L7), nearly identical to Rpl7Bp
  SMK1 and RPS1A
Description
Ribosomal protein S1 (rp10; rat S3A), nearly identical to Rps1Bp
  SMK1 and RPS1B
Description
Ribosomal protein S1 (rp10; rat S3A), nearly identical to Rps1Ap
  SMK1 and RPS21A
Description
Ribosomal protein S21 (yeast S26; YS25; rat S21), identical to Rps21Bp
  SMK1 and RPS22B
Description
RIbosomal protein S22 (yeast S24; rp50; YS22; rat S15A), nearly identical to Rps22Ap
  SMK1 and RPS28A
Description
Ribosomal protein S28 (yeast S33; YS27; mammalian S28), nearly identical to Rps28Bp
  SMK1 and RPS30B
Description
Ribosomal protein S30B (mammalian S30), identical to Rps30Ap
  SMK1 and RPS31
Description
Fusion protein comprised of ribosomal protein S31 at the C-terminal half fused to ubiquitin at the N-terminal half (yeast S37)
  SMK1 and RPS5
Description
Ribosomal protein Rps5p (rp14; YS8; S2; mammalian S5) of the small subunit

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