About

The 2nd quantum revolution promises lossless electronics and fault-tolerant quantum computers—but key materials and devices are still missing. Shafayat's Q MIND Lab aims to bridge that gap and turn quantum potential into real-world technology.

Research topics

• Biology
• Genetics
• Computational biology

Selected publications

• Introns in yeast regulate translation to generate protein and cellular function

  The FASEB Journal · 2022

  1st authorCorresponding
  • Biology
  • Genetics
  • Computational biology

  While RNA splicing has been recognized as an important mode of eukaryotic gene regulation, the role that introns themselves play in gene expression and proteome diversity has been less clear. Here, we describe how the intron of GCR1 , a transcription factor that regulates glycolytic gene expression, contains intronic elements that control translation initiated from an in‐frame, intronic‐AUG. Moreover, the intronic elements regulate translation under stress conditions. To understand how the translation start site within the intron is recognized, we analyzed the structures and functions of sequences around the start site. These studies reveal an internal ribosome entry site (IRES) that regulates translation initiation from within the intron. In addition to this sequence, we find that a ribosomal protein, Rps25, regulates utilization of the intronic AUG. These data suggest that splicing regulation and intron retention set up a novel mode of translational control. When we analyzed all intron‐containing genes in yeast, we discovered that this architecture—an intronic AUG that is in frame with the annotated stop codon—is found in other intron‐containing genes. Moreover, the proteins generated appear to be functional, particularly under stress conditions. Together these studies illustrate a role for introns in translational control and tuning the proteome in response to environmental conditions.

  PublisherDOI

• CRISPR-Cas9: A fascinating journey from bacterial immune system to human gene editing

  Progress in molecular biology and translational science · 2021 · 42 citations

  1st authorCorresponding
  • Biology
  • Computational biology
  • Genetics
  PublisherDOI

• Sequence Elements in Yeast Introns Regulate Translation to Make Functional Proteins

  The FASEB Journal · 2020

  1st authorCorresponding
  • Biology
  • Genetics

  RNA splicing is an important mode of eukaryotic gene regulation. By the process of splicing, introns are excised from the pre‐mRNA and exons are ligated to make a mature message, which is then translated to make protein. In eukaryotes, introns play a key role in alternative splicing whereby alternative exons are ligated to make different mRNAs from the same pre‐RNA transcript. These mRNAs can, in turn, be translated to make different protein isoforms and increase protein diversity. Here, we explore a unique role for inefficiently‐spliced introns. Previously, we showed that an intron‐retained isoform of GCR1 encodes a protein which is initiated from an in‐frame intronic AUG. We have identified regulatory sequences upstream of the AUG that control translation from the intronic translation start site. Furthermore, we show that Rps25, a small ribosomal protein subunit, regulates utilization of the intronic AUG to facilitate the expression of the protein and control the relative levels of the two Gcr1p isoforms—one from the spliced RNA and one from the unspliced RNA. In light of this result, we next analyzed the introns of all known intron‐containing genes to assess whether other introns contain an AUG that is in‐frame with the same stop codon as the spliced isoform. We have identified and tested several such genes to determine whether the intronic AUGs direct protein expression and find that, indeed, they do. Moreover, when cells deleted of these genes express only the intron‐retained isoform, this restores viability to sick cells, suggesting that the proteins produced by intron retention are functional. These studies demonstrate a unique role for introns in regulating alternative isoform production to generate functionally important protein diversity. Support or Funding Information This work was supported by the National Science Foundation (BIO/MCB 1518316 to T.L.J) and National Institute of General Medical Sciences (GM‐085474 to T.L.J)

  PublisherDOI

• Pre‐mRNA splicing, histone modification, and the coordinated control of gene expression

  The FASEB Journal · 2017-04-01

  articleSenior author

  The emergence of whole genome and whole transcriptome sequencing has highlighted the need to explore new models to explain complex patterns of gene expression. For example, there has been a deepened appreciation for the role of diverse RNAs and their highly regulated processing in key cellular functions. Every step in the life cycle of an RNA—from its synthesis and processing to its export and translation—is subject to regulation. Recent studies have revealed that an added layer of regulation comes from the coupling and coordination of these reactions. RNA splicing, for example, occurs co‐transcriptionally, raising important questions about the interplay between transcription, chromatin, and the spliceosome as the cell regulates gene expression to adapt to a variety of environmental conditions. Despite its relatively streamlined genome, there are important examples of regulated splicing in Saccharomyces cerevisiae that provide mechanistic insights into the coordination of nuclear processes. We previously demonstrated that intron retention (a phenomenon that is common in higher eukaryotes) plays a crucial role in the yeast cell's ability to execute the proper gene expression program in response to nutrient deprivation (Hossain, M.A., Claggett, J. et al. Molecular Cell 2016). The glycolytic transcription factor Gcr1 (GlyColysis regulator 1) controls expression of over 75% of the genes in actively growing yeast, and GCR1 RNA contains a highly conserved intron, which allows the cell to generate multiple RNA isoforms whose levels and ratios change upon glucose depletion. One of these isoforms containing the retained intron is translated from a start site within the intron, raising important questions about regulation of GCR1 splicing, export of the intron‐containing GCR1 RNA, escape of the RNA from the cytoplasmic surveillance machinery, and the mechanism of its translation from different translation start sites. Additionally, synthesis of GCR1 is tightly regulated, including the regulated utilization of alternative transcription start sites that direct the synthesis of RNAs to make functional proteins. Hence, GCR1 regulation reveals intriguing RNA processing mechanisms. Here we show a role for chromatin modification in both the synthesis and processing of GCR1 RNA and define the features of GCR 1 that influence its regulation. Based on these results, we have analyzed the yeast transcriptome under a variety of conditions to assess the pervasiveness of these mechanisms in yeast cells. These results reveal common themes that govern the coordinated regulation of gene expression processes. Support or Funding Information This work was funded by: Howard Hughes Medical Institute Professors Program grant # 52008140 The National Science Foundation MCB‐1051921 NIH GM‐085474

  PublisherDOI

• Posttranscriptional Regulation of Gcr1 Expression and Activity Is Crucial for Metabolic Adjustment in Response to Glucose Availability

  Molecular Cell · 2016-05-01 · 40 citations

  articleOpen access1st author
  PublisherOA PDFDOI

• A deletion mutant ndv200 of the Bacillus thuringiensis vip3BR insecticidal toxin gene is a prospective candidate for the next generation of genetically modified crop plants resistant to lepidopteran insect damage

  Planta · 2015-04-25 · 17 citations

  article
  PublisherDOI

• Using Yeast Genetics to Study Splicing Mechanisms

  Methods in molecular biology · 2014-01-01 · 7 citations

  article1st authorCorresponding

  Pre-mRNA splicing is a critical step in eukaryotic gene expression, which involves removal of noncoding intron sequences from pre-mRNA and ligation of the remaining exon sequences to make a mature message. Splicing is carried out by a large ribonucleoprotein complex called the spliceosome. Since the first description of the pre-mRNA splicing reaction in the 1970s, elegant genetic and biochemical studies have revealed that the enzyme that catalyzes the reaction, the spliceosome, is an exquisitely dynamic macromolecular machine, and its RNA and protein components undergo highly ordered, tightly coordinated rearrangements in order to carry out intron recognition and splicing catalysis. Studies using the genetically tractable unicellular eukaryote budding yeast (Saccharomyces cerevisiae) have played an instrumental role in deciphering splicing mechanisms. In this chapter, we discuss how yeast genetics has been used to deepen our understanding of the mechanism of splicing and explore the potential for future mechanistic insights using S. cerevisiae as an experimental tool.

  PublisherDOI

• Variant cry1Ab entomocidal Bacillus thuringiensis toxin gene facilitates the recovery of an increased number of lepidopteran insect resistant independent rice transformants against yellow stem borer (Scirpophaga incertulus) inflicted damage

  Journal of Plant Biochemistry and Biotechnology · 2013-01-31 · 4 citations

  article
  PublisherDOI

• Autoregulation of SUS1: a splicing dependent regulation of histone H2B ubiquitination

  The FASEB Journal · 2012-04-01

  article1st authorCorresponding

  Pre‐messenger RNA splicing is an underappreciated mechanism for regulating gene expression in yeast ( Saccharomyces cerevisiae ), likely due to the paucity of intron containing genes in this single‐celled eukaryote. However, a growing number of studies suggest that introns play an important role in modulating gene expression under stress conditions. Recently, we have shown that environmental stress modulates splicing of the SUS1 , a two‐intron gene in yeast. Sus1p, which is a part of deubiquitination module within the SAGA complex, plays an important role in maintaining proper cellular levels of ubiquitinated H2B. The first intron of SUS1 contains non‐canonical 5’SS and branch point sequences, which leads to retention of the first intron and subsequently limits the production of SUS1 mRNA. Here, we show that increased accumulation of the first intron containing transcript leads to a decrease in SUS1 mRNA production. Interestingly, the first intron containing transcript can be translated to produce truncated Sus1 protein which appears to play a role in SUS1 autoregulation. This study hints at an autoregulatory mechanism of control of SUS1 splicing and demonstrates an important role for regulated splicing in yeast to control histone modification. National Science Foundation awards (NSF CAREER MCB‐0448010 and MCB‐1051921); National Institutes of Health (GM085474)

  PublisherDOI

• The Yeast Cap Binding Complex Modulates Transcription Factor Recruitment and Establishes Proper Histone H3K36 Trimethylation during Active Transcription

  Molecular and Cellular Biology · 2012-12-11 · 31 citations

  articleOpen access1st authorCorresponding

  Recent studies have revealed a close relationship between transcription, histone modification, and RNA processing. In fact, genome-wide analyses that correlate histone marks with RNA processing signals raise the possibility that specific RNA processing factors may modulate transcription and help to "write" chromatin marks. Here we show that the nuclear cap binding complex (CBC) directs recruitment of transcription elongation factors and establishes proper histone marks during active transcription. A directed genetic screen revealed that deletion of either subunit of the CBC confers a synthetic growth defect when combined with deletion of genes encoding either Ctk2 or Bur2, a component of the Saccharomyces cerevisiae ortholog of P-TEFb. The CBC physically associates with these complexes to recruit them during transcription and mediates phosphorylation at Ser-2 of the C-terminal domain (CTD) of RNA polymerase II. To understand how these interactions influence downstream events, histone H3K36me3 was examined, and we demonstrate that CBCΔ affects proper Set2-dependent H3K36me3. Consistent with this, the CBC and Set2 have similar effects on the ability to rapidly induce and sustain activated gene expression, and these effects are distinct from other histone methyltransferases. This work provides evidence for an emerging model that RNA processing factors can modulate the recruitment of transcription factors and influence histone modification during elongation.

  PublisherOA PDFDOI

Frequent coauthors

• Tracy Johnson

  University of Indianapolis

  10 shared

• Chandi C. Mandal

  Central University of Rajasthan

  7 shared

• Soumitra K. Sen

  5 shared

• Srimonta Gayen

  4 shared

• Anannya Banga

  4 shared

• Abhijit Dandapat

  Editas Medicine (United States)

  4 shared

• Asitava Basu

  Indian Institute of Technology Kharagpur

  3 shared

• Rajeswari Mukherjee

  Bose Institute

  2 shared

Labs

• Shafayat's Q MIND LabPI

Awards & honors

• APS Forum on International Physics & Forum on Early Career S…
• APS Division of Materials Physics Ovshinsky Student Travel A…
• Princeton School of Engineering and Applied Science Award fo…
• Institute for Complex Adaptive Matter QuantEmX Scientific Ex…
• First-Year Fellowship in Natural Sciences and Engineering, P…