David Bartel

Last updated
David P. Bartel
Nationality American
Alma mater Goshen College, Harvard University
Known for MicroRNAs
Awards Grand Prix scientifique de la Fondation Louis D. (2005)
NAS Award in Molecular Biology (2005)
Scientific career
Fields Biochemistry, Molecular Biology
Institutions Whitehead Institute, Massachusetts Institute of Technology
Thesis RNA recognition and catalysis : I. New ribozymes from random sequences ; II. The HIV rev-RRE interaction (1993)
Doctoral advisor Jack Szostak

David P. Bartel is an American molecular biologist best known for his work on microRNAs. Bartel is a Professor of Biology at the Massachusetts Institute of Technology, Member of the Whitehead Institute, and investigator of the Howard Hughes Medical Institute (HHMI).

Contents

Biography

Bartel earned his B.A. degree in biology from Goshen College in 1982 and his Ph.D. degree in virology from Harvard University in 1993, under the mentorship of Jack W. Szostak. [1]

While in the Szostak lab, Bartel isolated the first ribozymes directly from random sequence, using in vitro evolution (among these, the Class I ligase). [2] After he became independent at the Whitehead Institute, he further evolved this ribozyme to function as a RNA-dependent RNA polymerase to extend primers on external RNA templates, bolstering the "RNA world" theory. [3] [4]

Bartel later shifted his research focus towards microRNA biology and in particular on understanding their regulatory functions. [5] MicroRNAs are short pieces of RNA, about 22 nucleotides long, that dampen gene expression through the silencing of messenger RNAs (mRNAs). His lab was one of three that found that animals have many of these small regulatory RNAs, [6] [7] [8] and he was the first to describe microRNAs in plants. [9] [10] Through his work with microRNAs, he developed a methodology that predicts their regulatory targets and created the web-based tool TargetScan, which makes these predictions available to the research community. [11] [12] [13] [14] [15] His research has also shown that most human mRNAs are regulated by microRNAs and that microRNAs predominantly act to decrease the levels of their mRNA targets. [13] [16]

Bartel also discovered several other types of regulatory RNAs, including heterochromatic siRNAs, which silence DNA instead of RNA. [17] In addition, Bartel is investigating the roles of long non-coding RNAs (lncRNAs) and how the untranslated regions and tails of mRNAs recruit and mediate regulatory phenomena. [5]

Bartel is a founder and a scientific advisor of Alnylam Pharmaceuticals, a company started in 2002 to advance “RNAi (RNA interference) therapeutics as a new class of innovative medicines”. [18]

In 2006, Bartel was placed second by Thomson Reuters in a 'citations' ranking in the field of Molecular Biology/Genetics. He has received several awards and was elected to the National Academy of Sciences in 2011. [19]

Related Research Articles

microRNA Small non-coding ribonucleic acid molecule

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then gene silence said mRNA molecules by one or more of the following processes:

  1. Cleavage of mRNA strand into two pieces,
  2. Destabilization of mRNA by shortening its poly(A) tail, or
  3. Translation of mRNA into proteins.
<span class="mw-page-title-main">Ribozyme</span> Type of RNA molecules

Ribozymes are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material and a biological catalyst, and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems.

Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence genes are being increasingly used to produce therapeutics to combat cancer and other diseases, such as infectious diseases and neurodegenerative disorders.

RNA silencing or RNA interference refers to a family of gene silencing effects by which gene expression is negatively regulated by non-coding RNAs such as microRNAs. RNA silencing may also be defined as sequence-specific regulation of gene expression triggered by double-stranded RNA (dsRNA). RNA silencing mechanisms are conserved among most eukaryotes. The most common and well-studied example is RNA interference (RNAi), in which endogenously expressed microRNA (miRNA) or exogenously derived small interfering RNA (siRNA) induces the degradation of complementary messenger RNA. Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA).

mir-46/mir-47/mir-281 microRNA precursor family

In molecular biology, mir-46 and mir-47 are microRNA expressed in C. elegans from related hairpin precursor sequences. The predicted hairpin precursor sequences for Drosophila mir-281 are also related and, hence, belong to this family. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequences are expressed from the 3' arms of the hairpin precursors.

mir-156 microRNA precursor

MicroRNA (miRNA) precursor miR156 is a family of plant non-coding RNA. This microRNA has now been predicted or experimentally confirmed in a range of plant species. Animal miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. miR156 functions in the induction of flowering by suppressing the transcripts of SQUAMOSA-PROMOTER BINDING LIKE (SPL) transcription factors gene family. It was suggested that the loading into ARGONAUTE1 and ARGONAUTE5 is required for miR156 functionality in Arabidopsis thaliana. In plants the precursor sequences may be longer, and the carpel factory (caf) enzyme appears to be involved in processing. In this case the mature sequence comes from the 5' arm of the precursor, and both Arabidopsis thaliana and rice genomes contain a number of related miRNA precursors which give rise to almost identical mature sequences. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The products are thought to have regulatory roles through complementarity to mRNA.

mir-160 microRNA precursor family

In molecular biology, mir-160 is a microRNA that has been predicted or experimentally confirmed in a range of plant species including Arabidopsis thaliana and Oryza sativa (rice). miR-160 is predicted to bind complementary sites in the untranslated regions of auxin response factor genes to regulate their expression. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 5' arm of the hairpin.

mir-219 microRNA precursor family

In molecular biology, the microRNA miR-219 was predicted in vertebrates by conservation between human, mouse and pufferfish and cloned in pufferfish. It was later predicted and confirmed experimentally in Drosophila. Homologs of miR-219 have since been predicted or experimentally confirmed in a wide range of species, including the platyhelminth Schmidtea mediterranea, several arthropod species and a wide range of vertebrates. The hairpin precursors are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 5' arm of the hairpin.

Post-transcriptional regulation is the control of gene expression at the RNA level. It occurs once the RNA polymerase has been attached to the gene's promoter and is synthesizing the nucleotide sequence. Therefore, as the name indicates, it occurs between the transcription phase and the translation phase of gene expression. These controls are critical for the regulation of many genes across human tissues. It also plays a big role in cell physiology, being implicated in pathologies such as cancer and neurodegenerative diseases.

<span class="mw-page-title-main">RNA interference</span> Biological process of gene regulation

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.

This microRNA database and microRNA targets databases is a compilation of databases and web portals and servers used for microRNAs and their targets. MicroRNAs (miRNAs) represent an important class of small non-coding RNAs (ncRNAs) that regulate gene expression by targeting messenger RNAs.

Christopher Boyce Burge is Professor of Biology and Biological Engineering at Massachusetts Institute of Technology.

In molecular biology, competing endogenous RNAs regulate other RNA transcripts by competing for shared microRNAs (miRNAs). Models for ceRNA regulation describe how changes in the expression of one or multiple miRNA targets alter the number of unbound miRNAs and lead to observable changes in miRNA activity - i.e., the abundance of other miRNA targets. Models of ceRNA regulation differ greatly. Some describe the kinetics of target-miRNA-target interactions, where changes in the expression of one target species sequester one miRNA species and lead to changes in the dysregulation of the other target species. Others attempt to model more realistic cellular scenarios, where multiple RNA targets are affecting multiple miRNAs and where each target pair is co-regulated by multiple miRNA species. Some models focus on mRNA 3' UTRs as targets, and others consider long non-coding RNA targets as well. It's evident that our molecular-biochemical understanding of ceRNA regulation remains incomplete.

mir-48 microRNA is a microRNA which is found in nematodes, in which it controls developmental timing. It acts in the heterochronic pathway, where it controls the timing of cell fate decisions in the vulva and hypodermis during larval development.

MicroRNA sequencing (miRNA-seq), a type of RNA-Seq, is the use of next-generation sequencing or massively parallel high-throughput DNA sequencing to sequence microRNAs, also called miRNAs. miRNA-seq differs from other forms of RNA-seq in that input material is often enriched for small RNAs. miRNA-seq allows researchers to examine tissue-specific expression patterns, disease associations, and isoforms of miRNAs, and to discover previously uncharacterized miRNAs. Evidence that dysregulated miRNAs play a role in diseases such as cancer has positioned miRNA-seq to potentially become an important tool in the future for diagnostics and prognostics as costs continue to decrease. Like other miRNA profiling technologies, miRNA-Seq has both advantages and disadvantages.

In molecular biology mir-241 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In bioinformatics, TargetScan is a web server that predicts biological targets of microRNAs (miRNAs) by searching for the presence of sites that match the seed region of each miRNA. For many species, other types of sites, known as 3'-compensatory sites are also identified. These miRNA target predictions are regularly updated and improved by the laboratory of David Bartel in conjunction with the Whitehead Institute Bioinformatics and Research Computing Group.

<span class="mw-page-title-main">MIR7-1</span> Non-coding RNA in the species Homo sapiens

MicroRNA 7-1 is a microRNA molecule that in humans is encoded by the MIR7-1 gene.

<span class="mw-page-title-main">MicroRNA 196a-2</span>

MicroRNA 196a-2 is a MicroRNA that in humans is encoded by the MIR196A2 gene, and is part of the Mir-196 microRNA precursor family.

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

The microprocessor complex is a protein complex involved in the early stages of processing microRNA (miRNA) and RNA interference (RNAi) in animal cells. The complex is minimally composed of the ribonuclease enzyme Drosha and the dimeric RNA-binding protein DGCR8, and cleaves primary miRNA substrates to pre-miRNA in the cell nucleus. Microprocessor is also the smaller of the two multi-protein complexes that contain human Drosha.

References

  1. ↑ "David P. Bartel '82". Goshen Bulletin. 2007. Retrieved 8 March 2014.
  2. ↑ Science. 1993 Sep 10;261(5127):1411-8. "Isolation of new ribozymes from a large pool of random sequences." Bartel DP, Szostak JW.
  3. ↑ Trends Cell Biol. 1999 Dec;9(12):M9-M13. "Constructing an RNA world." Bartel DP, Unrau PJ.
  4. ↑ Johnston, WK; Unrau, PJ; Lawrence, MS; Glasner, ME; Bartel, DP (18 May 2001). "RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension". Science. 292 (5520): 1319–25. Bibcode:2001Sci...292.1319J. CiteSeerX   10.1.1.70.5439 . doi:10.1126/science.1060786. PMID   11358999. S2CID   14174984.
  5. 1 2 "David Bartel". HHMI. Retrieved 7 October 2016.
  6. ↑ "Science". 2001 Oct 26;294(5543):853-8. "Identification of novel genes coding for small expressed RNAs." Lagos-Quintana M1, Rauhut R, Lendeckel W, Tuschl T.
  7. ↑ "Science". 2001 Oct 26;294(5543):858-62. "An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans." Lau NC1, Lim LP, Weinstein EG, Bartel DP.
  8. ↑ "Science". 2001 Oct 26;294(5543):862-4. "An extensive class of small RNAs in Caenorhabditis elegans. Lee RC1, Ambros V.
  9. ↑ "Genes Dev." 2002 Jul 1;16(13):1616-26. "MicroRNAs in plants." Reinhart BJ1, Weinstein EG, Rhoades MW, Bartel B, Bartel DP.
  10. ↑ "Cell". 2002 Aug 23;110(4):513-20. "Prediction of plant microRNA targets." Rhoades MW1, Reinhart BJ, Lim LP, Burge CB, Bartel B, Bartel DP.
  11. ↑ "Cell". 2005 Jan 14;120(1):15-20. "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets." Lewis BP, Burge CB, Bartel DP.
  12. ↑ "Mol Cell". 2007 Jul 6;27(1):91-105. "MicroRNA targeting specificity in mammals: determinants beyond seed pairing." Grimson A1, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP.
  13. 1 2 "Genome Res." 2009 Jan;19(1):92-105. "Most mammalian mRNAs are conserved targets of microRNAs." Friedman RC1, Farh KK, Burge CB, Bartel DP.
  14. ↑ Agarwal, Vikram; Bell, George W.; Nam, Jin-Wu; Bartel, David P. (2015-08-12). "Predicting effective microRNA target sites in mammalian mRNAs". eLife. 4: e05005. doi: 10.7554/eLife.05005 . ISSN   2050-084X. PMC   4532895 . PMID   26267216.
  15. ↑ Agarwal, V; Subtelny, AO; Thiru, P; Ulitsky, I; Bartel, DP (4 October 2018). "Predicting microRNA targeting efficacy in Drosophila". Genome Biology. 19 (1): 152. doi: 10.1186/s13059-018-1504-3 . PMC   6172730 . PMID   30286781.
  16. ↑ Guo, H; Ingolia, NT; Weissman, JS; Bartel, DP (12 August 2010). "Mammalian microRNAs predominantly act to decrease target mRNA levels". Nature. 466 (7308): 835–40. Bibcode:2010Natur.466..835G. doi:10.1038/nature09267. PMC   2990499 . PMID   20703300.
  17. ↑ Reinhart, BJ; Bartel, DP (13 September 2002). "Small RNAs correspond to centromere heterochromatic repeats". Science. 297 (5588): 1831. doi:10.1126/science.1077183. PMID   12193644. S2CID   42288846.
  18. ↑ "Scientific Advisory Board". Alnylam.com. Retrieved 5 October 2016.
  19. ↑ "Whitehead Member David Bartel elected to National Academy of Sciences" . Retrieved 25 January 2015.
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