Satarupa Das - Academia.edu (original) (raw)
Papers by Satarupa Das
In Saccharomyces cerevisiae, DRN (Decay of RNA in the Nucleus) requiring Cbc1/2p, Tif4631p, and U... more In Saccharomyces cerevisiae, DRN (Decay of RNA in the Nucleus) requiring Cbc1/2p, Tif4631p, and Upf3p promotes the exosomal degradation of aberrantly long 3′-extended-, export-defective transcripts and a small group of normal (special) mRNAs. In this study, using a systematic proteomic analysis we show that each of the known components interacts with one another and they exist as a separate complex, which was dubbed CTEXT (CBC-Tif4631p-dependent EXosome Targeting). We also identified a DEAD-box RNA helicase Dbp2p as an additional novel component of CTEXT during this analysis which was further bolstered by the finding that genomic deletions of Dbp2p led to the stabilization of all the signature nuclear messages. Interestingly, the RRM domain of Tif4631p located at the extreme N-termini of this polypeptide was found to play a vital role in in mediating the interaction of the CTEXT with the core exosome complex. These inferences were substantiated by the finding that deletion of this d...
FEMS Yeast Research, 2014
Messenger RNAs retained in the nucleus of Saccharomyces cerevisiae are subjected to a degradation... more Messenger RNAs retained in the nucleus of Saccharomyces cerevisiae are subjected to a degradation system designated DRN (Degradation of mRNA in the Nucleus) that is dependent on the nuclear mRNA cap-binding protein, Cbc1p, as well as nuclear exosome component Rrp6p, a 3 0 to 5 0 exoribonuclease. DRN has been shown to act on RNAs preferentially retained in the nucleus, such as: (1) global mRNAs in export defective nup116-D mutant strains at the restrictive temperature; (2) a certain class of normal mRNAs called special mRNAs (e.g. IMP3 and YLR194c mRNAs); and (3) mutant mRNAs for example, lys2-187 and cyc1-512. In this study, we further identify three novel components of DRN (Cbc2p, Upf3p and Tif4631p) by employing a genetic screen and by considering proteins/factors that interact with Cbc1p. Participation of these components in DRN was confirmed by demonstrating that null alleles of these genes resulted in stabilization of the rapid decay of global mRNAs in the export defective nup116-D strain and of representative special mRNAs. Depletion of Tif4632p, an isoform of Tif4631p, also exhibited a partial impairment of DRN function and is therefore also considered to play a functional role in DRN. These findings clearly establish that CBC2, UPF3, and TIF4631/32 gene products participate in DRN function.
Proceedings of the National Academy of Sciences, 2006
We previously demonstrated that mRNAs retained in the nucleus of Saccharomyces cerevisiae are sub... more We previously demonstrated that mRNAs retained in the nucleus of Saccharomyces cerevisiae are subjected to a degradation system-designated DRN (degradation of mRNA in the nucleus), that is diminished in cbc1 -Δ or cbc2 -Δ mutants lacking components of the cap-binding complex and in rrp6 -Δ mutants lacking Rrp6p, a 3′ to 5′ nuclear exonuclease. Two mutants, lys2-187 and lys2-121 , were uncovered by screening numerous lys2 mutants for suppression by cbc1 -Δ and rrp6 -Δ. Both mutants were identical and contained the two base changes, one of which formed a TGA nonsense codon. LYS2 mRNAs from the lys2-187 and related mutants were rapidly degraded, and the degradation was suppressed by cbc1 -Δ and rrp6 -Δ. The U1A-GFP imaging procedure was used to show that the lys2-187 mRNA was partially retained in the nucleus, explaining the susceptibility to DRN. The creation of several derivatives of lys2-187 by site-directed mutagenesis revealed that the in-frame TGA by itself was not responsible fo...
Journal of Biosciences, 2013
Efficient production of translation-competent mRNAs involves processing and modification events b... more Efficient production of translation-competent mRNAs involves processing and modification events both in the nucleus and cytoplasm which require a number of complex machineries at both co-transcriptional and posttranscriptional levels. Mutations in the genomic sequence sometimes result in the formation of mutant nonfunctional defective messages. In addition, the enormous amounts of complexities involved in the biogenesis of mRNPs in the nucleus very often leads to the formation of aberrant and faulty messages along with their functional counterpart. Subsequent translation of these mutant and defective populations of messenger RNAs could possibly result in the unfaithful transmission of genetic information and thus is considered a threat to the survival of the cell. To prevent this possibility, mRNA quality control systems have evolved both in the nucleus and cytoplasm in eukaryotes to scrutinize various stages of mRNP biogenesis and translation. In this review, we will focus on the physiological role of some of these mRNA quality control systems in the simplest model eukaryote Saccharomyces cerevisiae.
Journal of Bacteriology, 2010
Abundant in milk and other dairy products, lactose is considered to have an important role in ora... more Abundant in milk and other dairy products, lactose is considered to have an important role in oral microbial ecology and can contribute to caries development in both adults and young children. To better understand the metabolism of lactose and galactose by Streptococcus mutans , the major etiological agent of human tooth decay, a genetic analysis of the tagatose-6-phosphate ( lac ) and Leloir ( gal ) pathways was performed in strain UA159. Deletion of each gene in the lac operon caused various alterations in expression of a P lacA -cat promoter fusion and defects in growth on either lactose ( lacA , lacB , lacF , lacE , and lacG ), galactose ( lacA , lacB , lacD , and lacG ) or both sugars ( lacA , lacB , and lacG ). Failure to grow in the presence of galactose or lactose by certain lac mutants appeared to arise from the accumulation of intermediates of galactose metabolism, particularly galatose-6-phosphate. The glucose- and lactose-PTS permeases, EII Man and EII Lac , respectively...
FEMS yeast research, Jan 29, 2016
The eukaryotic translation initiation factor, eIF4G plays a key functional role in the initiation... more The eukaryotic translation initiation factor, eIF4G plays a key functional role in the initiation of cap-dependent translation by acting as an adapter to nucleate the assembly of eIF4F complex. Together with poly(A) binding protein and eIF3, eIF4F subsequently triggers the recruitment of 43S ribosomal pre-initiation complex to the messenger RNA template. Since eukaryotes primarily regulate translation at the level of initiation, eIF4G is implicated in the control of eukaryotic gene expression. Remarkably, emerging evidence in Saccharomyces cerevisiae indicates that eIF4G also plays a key role in nuclear mRNA biogenesis and surveillance - a finding that is in agreement with its nuclear distribution. Here, we focus on the functional involvement of eIF4G in the nucleus in modulating pre-mRNA splicing, mRNA surveillance, and possibly in much-debated nuclear translation. Notably, the nature of the biochemical role of this protein in the major events of cellular mRNA metabolism emphasizes...
In Saccharomyces cerevisiae, DRN (Decay of RNA in the Nucleus) requiring Cbc1/2p, Tif4631p, and U... more In Saccharomyces cerevisiae, DRN (Decay of RNA in the Nucleus) requiring Cbc1/2p, Tif4631p, and Upf3p promotes the exosomal degradation of aberrantly long 3′-extended-, export-defective transcripts and a small group of normal (special) mRNAs. In this study, using a systematic proteomic analysis we show that each of the known components interacts with one another and they exist as a separate complex, which was dubbed CTEXT (CBC-Tif4631p-dependent EXosome Targeting). We also identified a DEAD-box RNA helicase Dbp2p as an additional novel component of CTEXT during this analysis which was further bolstered by the finding that genomic deletions of Dbp2p led to the stabilization of all the signature nuclear messages. Interestingly, the RRM domain of Tif4631p located at the extreme N-termini of this polypeptide was found to play a vital role in in mediating the interaction of the CTEXT with the core exosome complex. These inferences were substantiated by the finding that deletion of this d...
FEMS Yeast Research, 2014
Messenger RNAs retained in the nucleus of Saccharomyces cerevisiae are subjected to a degradation... more Messenger RNAs retained in the nucleus of Saccharomyces cerevisiae are subjected to a degradation system designated DRN (Degradation of mRNA in the Nucleus) that is dependent on the nuclear mRNA cap-binding protein, Cbc1p, as well as nuclear exosome component Rrp6p, a 3 0 to 5 0 exoribonuclease. DRN has been shown to act on RNAs preferentially retained in the nucleus, such as: (1) global mRNAs in export defective nup116-D mutant strains at the restrictive temperature; (2) a certain class of normal mRNAs called special mRNAs (e.g. IMP3 and YLR194c mRNAs); and (3) mutant mRNAs for example, lys2-187 and cyc1-512. In this study, we further identify three novel components of DRN (Cbc2p, Upf3p and Tif4631p) by employing a genetic screen and by considering proteins/factors that interact with Cbc1p. Participation of these components in DRN was confirmed by demonstrating that null alleles of these genes resulted in stabilization of the rapid decay of global mRNAs in the export defective nup116-D strain and of representative special mRNAs. Depletion of Tif4632p, an isoform of Tif4631p, also exhibited a partial impairment of DRN function and is therefore also considered to play a functional role in DRN. These findings clearly establish that CBC2, UPF3, and TIF4631/32 gene products participate in DRN function.
Proceedings of the National Academy of Sciences, 2006
We previously demonstrated that mRNAs retained in the nucleus of Saccharomyces cerevisiae are sub... more We previously demonstrated that mRNAs retained in the nucleus of Saccharomyces cerevisiae are subjected to a degradation system-designated DRN (degradation of mRNA in the nucleus), that is diminished in cbc1 -Δ or cbc2 -Δ mutants lacking components of the cap-binding complex and in rrp6 -Δ mutants lacking Rrp6p, a 3′ to 5′ nuclear exonuclease. Two mutants, lys2-187 and lys2-121 , were uncovered by screening numerous lys2 mutants for suppression by cbc1 -Δ and rrp6 -Δ. Both mutants were identical and contained the two base changes, one of which formed a TGA nonsense codon. LYS2 mRNAs from the lys2-187 and related mutants were rapidly degraded, and the degradation was suppressed by cbc1 -Δ and rrp6 -Δ. The U1A-GFP imaging procedure was used to show that the lys2-187 mRNA was partially retained in the nucleus, explaining the susceptibility to DRN. The creation of several derivatives of lys2-187 by site-directed mutagenesis revealed that the in-frame TGA by itself was not responsible fo...
Journal of Biosciences, 2013
Efficient production of translation-competent mRNAs involves processing and modification events b... more Efficient production of translation-competent mRNAs involves processing and modification events both in the nucleus and cytoplasm which require a number of complex machineries at both co-transcriptional and posttranscriptional levels. Mutations in the genomic sequence sometimes result in the formation of mutant nonfunctional defective messages. In addition, the enormous amounts of complexities involved in the biogenesis of mRNPs in the nucleus very often leads to the formation of aberrant and faulty messages along with their functional counterpart. Subsequent translation of these mutant and defective populations of messenger RNAs could possibly result in the unfaithful transmission of genetic information and thus is considered a threat to the survival of the cell. To prevent this possibility, mRNA quality control systems have evolved both in the nucleus and cytoplasm in eukaryotes to scrutinize various stages of mRNP biogenesis and translation. In this review, we will focus on the physiological role of some of these mRNA quality control systems in the simplest model eukaryote Saccharomyces cerevisiae.
Journal of Bacteriology, 2010
Abundant in milk and other dairy products, lactose is considered to have an important role in ora... more Abundant in milk and other dairy products, lactose is considered to have an important role in oral microbial ecology and can contribute to caries development in both adults and young children. To better understand the metabolism of lactose and galactose by Streptococcus mutans , the major etiological agent of human tooth decay, a genetic analysis of the tagatose-6-phosphate ( lac ) and Leloir ( gal ) pathways was performed in strain UA159. Deletion of each gene in the lac operon caused various alterations in expression of a P lacA -cat promoter fusion and defects in growth on either lactose ( lacA , lacB , lacF , lacE , and lacG ), galactose ( lacA , lacB , lacD , and lacG ) or both sugars ( lacA , lacB , and lacG ). Failure to grow in the presence of galactose or lactose by certain lac mutants appeared to arise from the accumulation of intermediates of galactose metabolism, particularly galatose-6-phosphate. The glucose- and lactose-PTS permeases, EII Man and EII Lac , respectively...
FEMS yeast research, Jan 29, 2016
The eukaryotic translation initiation factor, eIF4G plays a key functional role in the initiation... more The eukaryotic translation initiation factor, eIF4G plays a key functional role in the initiation of cap-dependent translation by acting as an adapter to nucleate the assembly of eIF4F complex. Together with poly(A) binding protein and eIF3, eIF4F subsequently triggers the recruitment of 43S ribosomal pre-initiation complex to the messenger RNA template. Since eukaryotes primarily regulate translation at the level of initiation, eIF4G is implicated in the control of eukaryotic gene expression. Remarkably, emerging evidence in Saccharomyces cerevisiae indicates that eIF4G also plays a key role in nuclear mRNA biogenesis and surveillance - a finding that is in agreement with its nuclear distribution. Here, we focus on the functional involvement of eIF4G in the nucleus in modulating pre-mRNA splicing, mRNA surveillance, and possibly in much-debated nuclear translation. Notably, the nature of the biochemical role of this protein in the major events of cellular mRNA metabolism emphasizes...