Paul Babitzke

Last updated
Paul Babitzke
Paul Babitzke.jpg
Alma mater St. Cloud State University
Scientific career
FieldsMolecular biology
Institutions Pennsylvania State University

Paul Babitzke is a professor of biochemistry and molecular biology and director of the Center for RNA Molecular Biology at Pennsylvania State University. [1] [2]

Contents

Education

Paul Babitzke obtained his B.A. in biomedical science from St. Cloud State University in Minnesota in 1994. [3] He earned his Ph.D. in genetics from the University of Georgia in 1991. [1]

Career

Before he started at Penn State University in 1994, Babitzke worked as a postdoctoral scientist at Stanford University's department of biological sciences for 3 years. [3] Currently, he is professor of biochemistry and molecular biology at Penn State. [1]

He became an assistant professor of biochemistry and molecular biology in 1994 and associate professor in 2000. In 2006, Babitzke was promoted to full professor. [4]

Since 2009, he has been serving as director of the Center for RNA Molecular Biology in the Penn State Huck Institutes of the Life Sciences. [5] His research focuses on the regulation of gene expression mediated by RNA polymerase pausing, transcription termination, RNA structure, and RNA-binding proteins.

In 2016, he was elected as Fellow of the American Association for the Advancement of Science. [1]

In 2017, he was elected as Fellow of the American Academy of Microbiology. [1]

Honors and awards

Selected publications

Related Research Articles

<span class="mw-page-title-main">Transcription (biology)</span> Process of copying a segment of DNA into RNA

Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins produce messenger RNA (mRNA). Other segments of DNA are transcribed into RNA molecules called non-coding RNAs (ncRNAs).

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.

<span class="mw-page-title-main">Rho factor</span> Prokaryotic protein

A ρ factor is a bacterial protein involved in the termination of transcription. Rho factor binds to the transcription terminator pause site, an exposed region of single stranded RNA after the open reading frame at C-rich/G-poor sequences that lack obvious secondary structure.

In genetics, a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription. This sequence mediates transcriptional termination by providing signals in the newly synthesized transcript RNA that trigger processes which release the transcript RNA from the transcriptional complex. These processes include the direct interaction of the mRNA secondary structure with the complex and/or the indirect activities of recruited termination factors. Release of the transcriptional complex frees RNA polymerase and related transcriptional machinery to begin transcription of new mRNAs.

<i>Bacillus subtilis</i> Catalase-positive bacterium

Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus Bacillus, B. subtilis is rod-shaped, and can form a tough, protective endospore, allowing it to tolerate extreme environmental conditions. B. subtilis has historically been classified as an obligate aerobe, though evidence exists that it is a facultative anaerobe. B. subtilis is considered the best studied Gram-positive bacterium and a model organism to study bacterial chromosome replication and cell differentiation. It is one of the bacterial champions in secreted enzyme production and used on an industrial scale by biotechnology companies.

In molecular biology, a termination factor is a protein that mediates the termination of RNA transcription by recognizing a transcription terminator and causing the release of the newly made mRNA. This is part of the process that regulates the transcription of RNA to preserve gene expression integrity and are present in both eukaryotes and prokaryotes, although the process in bacteria is more widely understood. The most extensively studied and detailed transcriptional termination factor is the Rho (ρ) protein of E. coli.

In genetics, attenuation is a regulatory mechanism for some bacterial operons that results in premature termination of transcription. The canonical example of attenuation used in many introductory genetics textbooks, is ribosome-mediated attenuation of the trp operon. Ribosome-mediated attenuation of the trp operon relies on the fact that, in bacteria, transcription and translation proceed simultaneously. Attenuation involves a provisional stop signal (attenuator), located in the DNA segment that corresponds to the leader sequence of mRNA. During attenuation, the ribosome becomes stalled (delayed) in the attenuator region in the mRNA leader. Depending on the metabolic conditions, the attenuator either stops transcription at that point or allows read-through to the structural gene part of the mRNA and synthesis of the appropriate protein.

<i>trp</i> operon Operon that codes for the components for production of tryptophan

The trp operon is a group of genes that are transcribed together, encoding the enzymes that produce the amino acid tryptophan in bacteria. The trp operon was first characterized in Escherichia coli, and it has since been discovered in many other bacteria. The operon is regulated so that, when tryptophan is present in the environment, the genes for tryptophan synthesis are repressed.

<span class="mw-page-title-main">Bacterial transcription</span>

Bacterial transcription is the process in which a segment of bacterial DNA is copied into a newly synthesized strand of messenger RNA (mRNA) with use of the enzyme RNA polymerase.

In the field of molecular biology the 6S RNA is a non-coding RNA that was one of the first to be identified and sequenced. What it does in the bacterial cell was unknown until recently. In the early 2000s scientists found out the function of 6S RNA to be as a regulator of sigma 70-dependent gene transcription. All bacterial RNA polymerases have a subunit called a sigma factor. The sigma factors are important because they control how DNA promoter binding and RNA transcription start sites. Sigma 70 was the first one to be discovered in Escherichia coli.

<span class="mw-page-title-main">Tryptophan operon leader</span>

The Tryptophan operon leader is an RNA element found at the 5′ of some bacterial tryptophan operons. The leader sequence can form two different structures known as the terminator and the anti-terminator, based on the Tryptophan amounts in the cell. The leader also codes for very short peptide sequence that is rich in tryptophan. The terminator structure is recognised as a termination signal for RNA polymerase and the operon is not transcribed. This structure forms when the cell has an excess of tryptophan and ribosome movement over the leader transcript is not impeded. When there is a deficiency of the charged tryptophanyl tRNA the ribosome translating the leader peptide stalls and the antiterminator structure can form. This allows RNA polymerase to transcribe the operon.

<span class="mw-page-title-main">CsrB/RsmB RNA family</span> Non-coding RNA molecule

The CsrB RNA is a non-coding RNA that binds to approximately 9 to 10 dimers of the CsrA protein. The CsrB RNAs contain a conserved motif CAGGXXG that is found in up to 18 copies and has been suggested to bind CsrA. The Csr regulatory system has a strong negative regulatory effect on glycogen biosynthesis, glyconeogenesis and glycogen catabolism and a positive regulatory effect on glycolysis. In other bacteria such as Erwinia carotovora the RsmA protein has been shown to regulate the production of virulence determinants, such extracellular enzymes. RsmA binds to RsmB regulatory RNA which is also a member of this family.

<span class="mw-page-title-main">T-box leader</span> RNA element

Usually found in gram-positive bacteria, the T box leader sequence is an RNA element that controls gene expression through the regulation of translation by binding directly to a specific tRNA and sensing its aminoacylation state. This interaction controls expression of downstream aminoacyl-tRNA synthetase genes, amino acid biosynthesis, and uptake-related genes in a negative feedback loop. The uncharged tRNA acts as the effector for transcription antitermination of genes in the T-box leader family. The anticodon of a specific tRNA base pairs to a specifier sequence within the T-box motif, and the NCCA acceptor tail of the tRNA base pairs to a conserved bulge in the T-box antiterminator hairpin.

<span class="mw-page-title-main">Intrinsic termination</span>

Intrinsic, or rho-independent termination, is a process to signal the end of transcription and release the newly constructed RNA molecule. In bacteria such as E. coli, transcription is terminated either by a rho-dependent process or rho-independent process. In the Rho-dependent process, the rho-protein locates and binds the signal sequence in the mRNA and signals for cleavage. Contrarily, intrinsic termination does not require a special protein to signal for termination and is controlled by the specific sequences of RNA. When the termination process begins, the transcribed mRNA forms a stable secondary structure hairpin loop, also known as a stem-loop. This RNA hairpin is followed by multiple uracil nucleotides. The bonds between uracil (rU) and adenine (dA) are very weak. A protein bound to RNA polymerase (nusA) binds to the stem-loop structure tightly enough to cause the polymerase to temporarily stall. This pausing of the polymerase coincides with transcription of the poly-uracil sequence. The weak adenine-uracil bonds lower the energy of destabilization for the RNA-DNA duplex, allowing it to unwind and dissociate from the RNA polymerase. Overall, the modified RNA structure is what terminates transcription.

<span class="mw-page-title-main">DSIF</span>

DSIF is a protein complex that can either negatively or positively affect transcription by RNA polymerase II. It can interact with the negative elongation factor (NELF) to promote the stalling of Pol II at some genes, which is called promoter proximal pausing. The pause occurs soon after initiation, once 20-60 nucleotides have been transcribed. This stalling is relieved by positive transcription elongation factor b (P-TEFb) and Pol II enters productive elongation to resume synthesis till finish. In humans, DSIF is composed of hSPT4 and hSPT5. hSPT5 has a direct role in mRNA capping which occurs while the elongation is paused.

In a screen of the Bacillus subtilis genome for genes encoding ncRNAs, Saito et al. focused on 123 intergenic regions (IGRs) over 500 base pairs in length, the authors analyzed expression from these regions. Seven IGRs termed bsrC, bsrD, bsrE, bsrF, bsrG, bsrH and bsrI expressed RNAs smaller than 380 nt. All the small RNAs except BsrD RNA were expressed in transformed Escherichia coli cells harboring a plasmid with PCR-amplified IGRs of B. subtilis, indicating that their own promoters independently express small RNAs. Under non-stressed condition, depletion of the genes for the small RNAs did not affect growth. Although their functions are unknown, gene expression profiles at several time points showed that most of the genes except for bsrD were expressed during the vegetative phase, but undetectable during the stationary phase. Mapping the 5' ends of the 6 small RNAs revealed that the genes for BsrE, BsrF, BsrG, BsrH, and BsrI RNAs are preceded by a recognition site for RNA polymerase sigma factor σA.

<span class="mw-page-title-main">Eps-Associated RNA element</span>

The eps-Associated RNA element is a conserved RNA motif associated with exopolysaccharide (eps) or capsule biosynthesis genes in a subset of bacteria classified within the order Bacillales. It was initially discovered in Bacillus subtilis, located between the second and third gene in the eps operon. Deletion of the EAR element impairs biofilm formation.

Rsa RNAs are non-coding RNAs found in the bacterium Staphylococcus aureus. The shared name comes from their discovery, and does not imply homology. Bioinformatics scans identified the 16 Rsa RNA families named RsaA-K and RsaOA-OG. Others, RsaOH-OX, were found thanks to an RNomic approach. Although the RNAs showed varying expression patterns, many of the newly discovered RNAs were shown to be Hfq-independent and most carried a C-rich motif (UCCC).

Transcription-translation coupling is a mechanism of gene expression regulation in which synthesis of an mRNA (transcription) is affected by its concurrent decoding (translation). In prokaryotes, mRNAs are translated while they are transcribed. This allows communication between RNA polymerase, the multisubunit enzyme that catalyzes transcription, and the ribosome, which catalyzes translation. Coupling involves both direct physical interactions between RNA polymerase and the ribosome, as well as ribosome-induced changes to the structure and accessibility of the intervening mRNA that affect transcription.

References

  1. 1 2 3 4 5 "Paul Babitzke elected as Fellow of the American Academy of Microbiology". psu.edu. Retrieved April 4, 2017.
  2. "Paul Babitzke". psu.edu. Retrieved April 4, 2017.
  3. 1 2 3 4 5 6 7 8 9 "Paul Babitzke - Eberly College of Science". science.psu.edu. Retrieved 1 October 2019.
  4. "Lab Alumni". sites.psu.edu. Retrieved 22 May 2019.
  5. "Paul Babitzke". www.huck.psu.edu. Retrieved 17 August 2020.
  6. "Professor Brian Thomas - Personal Psu - Penn State". www.personal.psu.edu. Retrieved 1 November 2016.
  7. Baker, Carol S.; Morozov, Igor; Suzuki, Kazushi; Romeo, Tony; Babitzke, Paul (June 2002). "CsrA regulates glycogen biosynthesis by preventing translation of glgC in Escherichia coli". Molecular Microbiology. 44 (6): 1599–1610. doi:10.1046/j.1365-2958.2002.02982.x. ISSN   0950-382X. PMID   12067347. S2CID   34798274.
  8. Yakhnin, Alexander V.; Babitzke, Paul (2002-08-20). "NusA-stimulated RNA polymerase pausing and termination participates in the Bacillus subtilis trp operon attenuation mechanism in vitro". Proceedings of the National Academy of Sciences. 99 (17): 11067–11072. Bibcode:2002PNAS...9911067Y. doi: 10.1073/pnas.162373299 . ISSN   0027-8424. PMC   123211 . PMID   12161562.
  9. Yakhnin, Alexander V.; Yakhnin, Helen; Babitzke, Paul (2006-11-17). "RNA polymerase pausing regulates translation initiation by providing additional time for TRAP-RNA interaction". Molecular Cell. 24 (4): 547–557. doi: 10.1016/j.molcel.2006.09.018 . ISSN   1097-2765. PMID   17114058.
  10. Yakhnin, Alexander V.; Yakhnin, Helen; Babitzke, Paul (2008-10-21). "Function of the Bacillus subtilis transcription elongation factor NusG in hairpin-dependent RNA polymerase pausing in the trp leader". Proceedings of the National Academy of Sciences of the United States of America. 105 (42): 16131–16136. Bibcode:2008PNAS..10516131Y. doi: 10.1073/pnas.0808842105 . ISSN   1091-6490. PMC   2571025 . PMID   18852477.
  11. Yakhnin, Helen; Yakhnin, Alexander V.; Baker, Carol S.; Sineva, Elena; Berezin, Igor; Romeo, Tony; Babitzke, Paul (August 2011). "Complex regulation of the global regulatory gene csrA: CsrA-mediated translational repression, transcription from five promoters by Eσ70 and Eσ(S), and indirect transcriptional activation by CsrA". Molecular Microbiology. 81 (3): 689–704. doi:10.1111/j.1365-2958.2011.07723.x. ISSN   1365-2958. PMC   3189700 . PMID   21696456.
  12. Yakhnin, Alexander V.; Baker, Carol S.; Vakulskas, Christopher A.; Yakhnin, Helen; Berezin, Igor; Romeo, Tony; Babitzke, Paul (February 2013). "CsrA activates flhDC expression by protecting flhDC mRNA from RNase E-mediated cleavage". Molecular Microbiology. 87 (4): 851–866. doi:10.1111/mmi.12136. ISSN   0950-382X. PMC   3567230 . PMID   23305111.
  13. Mondal, Smarajit; Yakhnin, Alexander V.; Sebastian, Aswathy; Albert, Istvan; Babitzke, Paul (2016-01-11). "NusA-dependent transcription termination prevents misregulation of global gene expression". Nature Microbiology. 1: 15007. doi:10.1038/nmicrobiol.2015.7. ISSN   2058-5276. PMC   5358096 . PMID   27571753.
  14. Potts, Anastasia H.; Vakulskas, Christopher A.; Pannuri, Archana; Yakhnin, Helen; Babitzke, Paul; Romeo, Tony (2017-11-17). "Global role of the bacterial post-transcriptional regulator CsrA revealed by integrated transcriptomics". Nature Communications. 8 (1): 1596. Bibcode:2017NatCo...8.1596P. doi:10.1038/s41467-017-01613-1. ISSN   2041-1723. PMC   5694010 . PMID   29150605.
  15. Yakhnin, A. V.; Fitzgerald, P. C.; McIntosh, C.; Yakhnin, H.; Kireeva, M.; Turek-Herman, J.; Mandell, Z. F.; Kashlev, M.; Babitzke, P. (2020). "Europe PMC". Proceedings of the National Academy of Sciences of the United States of America. 117 (35): 21628–21636. doi: 10.1073/pnas.2006873117 . PMC   7474616 . PMID   32817529.
  16. Mandell, Zachary F.; Oshiro, Reid T.; Yakhnin, Alexander V.; Vishwakarma, Rishi; Kashlev, Mikhail; Kearns, Daniel B.; Babitzke, Paul (2021-04-09). "NusG is an intrinsic transcription termination factor that stimulates motility and coordinates gene expression with NusA". eLife. 10. doi: 10.7554/eLife.61880 . PMC   8060035 . PMID   33835023.