James L. Manley

Last updated
James L Manley
Dr James L Manley.JPG
Born (1949-11-30) November 30, 1949 (age 72)
Nationality American
Citizenship United States of America
Alma mater Columbia University BS in Biology (1971), Stony Brook University PhD (1976)
Scientific career
Fields Biology
Institutions Columbia University
Website http://biology.columbia.edu/people/manley

James Manley is the Julian Clarence Levi Professor of Life Sciences at Columbia University, where his laboratory studies gene expression in mammalian cells. [1] Manley and colleagues identified and characterized the key factors responsible for polyadenylation of mRNA precursors, and elucidated how this remarkably complex machinery functions in gene regulation, for example during cell growth and differentiation. He has also studied the mechanism and regulation of the process by which introns are removed from mRNA precursors, mRNA splicing. Manley and his coworkers codiscovered the first alternative splicing factor (SR protein), characterized how this and other splicing regulatory proteins function and are themselves regulated, showed how alternative splicing can become deregulated in disease, and with respect to mechanism demonstrated that two spliceosomal small nuclear RNAs by themselves have catalytic activity. Finally, he elucidated unexpected links between these mRNA processing reactions and transcription, DNA damage signaling and maintenance of genomic stability. His work has thus provided considerable insight into the complex mechanisms that are essential for the regulated production of mRNAs in mammalian cells.

Contents

Career

Manley received a B.S. from Columbia University, Ph.D. from Stony Brook/Cold Spring Harbor Labs, and did postdoctoral work at MIT. He has been in the Department of Biological Sciences at Columbia University since 1980, was Chair from 1995-2001 and Julian Clarence Levi Professor of Life Sciences since 1995. His research interests center on understanding the mechanisms and regulation of gene expression in mammalian cells. His work has been supported by many grants, including an NIH MERIT Award. He has authored or coauthored over 350 research articles and reviews on these topics, and is an ISI Highly Cited Researcher. Dr. Manley is or has been an Editor of three journals and has served on numerous editorial boards and review panels. He is a Fellow of the American Academy of Microbiology, the American Academy of Arts and Sciences and the American Association for the Advancement of Science, and a member of the National Academy of Sciences. [2] [3]

Related Research Articles

Non-coding RNA Class of ribonucleic acid that is not translated into proteins

A non-coding RNA (ncRNA) is an RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR.

Alternative splicing Process by which a single gene can code for multiple proteins

Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions. Notably, alternative splicing allows the human genome to direct the synthesis of many more proteins than would be expected from its 20,000 protein-coding genes.

Protein isoform

A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments (exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein.

SR protein

SR proteins are a conserved family of proteins involved in RNA splicing. SR proteins are named because they contain a protein domain with long repeats of serine and arginine amino acid residues, whose standard abbreviations are "S" and "R" respectively. SR proteins are ~200-600 amino acids in length and composed of two domains, the RNA recognition motif (RRM) region and the RS domain. SR proteins are more commonly found in the nucleus than the cytoplasm, but several SR proteins are known to shuttle between the nucleus and the cytoplasm.

Primary transcript RNA produced by transcription

A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs are modified in preparation for translation. For example, a precursor mRNA (pre-mRNA) is a type of primary transcript that becomes a messenger RNA (mRNA) after processing.

A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

Tom Maniatis, is an American professor of molecular and cellular biology. He is a Professor at Columbia University, and serves as the Scientific Director and CEO of the New York Genome Center.

The Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research is awarded by Brandeis University. It was established in 1971 "as an expression of the conviction that educational institutions have an important role to play in the encouragement and development of basic science as it applies to medicine".

RNA-binding proteins are proteins that bind to the double or single stranded RNA in cells and participate in forming ribonucleoprotein complexes. RBPs contain various structural motifs, such as RNA recognition motif (RRM), dsRNA binding domain, zinc finger and others. They are cytoplasmic and nuclear proteins. However, since most mature RNA is exported from the nucleus relatively quickly, most RBPs in the nucleus exist as complexes of protein and pre-mRNA called heterogeneous ribonucleoprotein particles (hnRNPs). RBPs have crucial roles in various cellular processes such as: cellular function, transport and localization. They especially play a major role in post-transcriptional control of RNAs, such as: splicing, polyadenylation, mRNA stabilization, mRNA localization and translation. Eukaryotic cells express diverse RBPs with unique RNA-binding activity and protein–protein interaction. According to the Eukaryotic RBP Database (EuRBPDB), there are 2961 genes encoding RBPs in humans. During evolution, the diversity of RBPs greatly increased with the increase in the number of introns. Diversity enabled eukaryotic cells to utilize RNA exons in various arrangements, giving rise to a unique RNP (ribonucleoprotein) for each RNA. Although RBPs have a crucial role in post-transcriptional regulation in gene expression, relatively few RBPs have been studied systematically.

Paraspeckle Cell compartment found in the nucleuss interchromatin space

In cell biology, a paraspeckle is an irregularly shaped compartment of the cell, approximately 0.2-1 μm in size, found in the nucleus' interchromatin space. First documented in HeLa cells, where there are generally 10-30 per nucleus, Paraspeckles are now known to also exist in all human primary cells, transformed cell lines and tissue sections. Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckle" refers to the splicing speckles to which they are always in close proximity. Their function is still not fully understood, but they are thought to regulate gene expression by sequestrating proteins or mRNAs with inverted repeats in their 3′ UTRs.

PER1

The PER1 gene encodes the period circadian protein homolog 1 protein in humans.

NRF1

Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor -like 1" which has an official symbol of NFE2L1.

Long non-coding RNA Non-protein coding transcripts longer than 200 nucleotides

Long non-coding RNAs are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of lncRNA which do not overlap protein-coding genes.

Serine/arginine-rich splicing factor 1

Serine/arginine-rich splicing factor 1 (SRSF1) also known as alternative splicing factor 1 (ASF1), pre-mRNA-splicing factor SF2 (SF2) or ASF1/SF2 is a protein that in humans is encoded by the SRSF1 gene. ASF/SF2 is an essential sequence specific splicing factor involved in pre-mRNA splicing. SRSF1 is the gene that codes for ASF/SF2 and is found on chromosome 17. The resulting splicing factor is a protein of approximately 33 kDa. ASF/SF2 is necessary for all splicing reactions to occur, and influences splice site selection in a concentration-dependent manner, resulting in alternative splicing. In addition to being involved in the splicing process, ASF/SF2 also mediates post-splicing activities, such as mRNA nuclear export and translation.

The NAS Award in Molecular Biology is awarded by the U.S. National Academy of Sciences "for recent notable discovery in molecular biology by a young scientist who is a citizen of the United States." It has been awarded annually since its inception in 1962.

The Selman A. Waksman Award in Microbiology is awarded by the U.S. National Academy of Sciences "in recognition of excellence in the field of microbiology." Named after Selman Waksman, it was first awarded in 1968. A $5000 prize is included in the honor.

David L. Spector

David L. Spector is a cell and molecular biologist best recognized for his research on gene expression and nuclear dynamics. He is currently a professor at Cold Spring Harbor Laboratory (CSHL) and head of the Gene Regulation and Cell Proliferation program of the CSHL Cancer Center. Since 2007, he has served as director of research of CSHL.

Michael Rosbash American geneticist and chronobiologist (born 1944)

Michael Morris Rosbash is an American geneticist and chronobiologist. Rosbash is a professor and researcher at Brandeis University and investigator at the Howard Hughes Medical Institute. Rosbash's research group cloned the Drosophila period gene in 1984 and proposed the Transcription Translation Negative Feedback Loop for circadian clocks in 1990. In 1998, they discovered the cycle gene, clock gene, and cryptochrome photoreceptor in Drosophila through the use of forward genetics, by first identifying the phenotype of a mutant and then determining the genetics behind the mutation. Rosbash was elected to the National Academy of Sciences in 2003. Along with Michael W. Young and Jeffrey C. Hall, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".

A chromatoid body is a dense structure in the cytoplasm of male germ cells. It is composed mainly of RNAs and RNA-binding proteins and is thus a type of RNP granule. Chromatoid body-like granules first appear in spermatocytes and condense into a single granule in round spermatids. The structure disappears again when spermatids start to elongate. The chromatoid body is crucial for spermatogenesis but its exact role in the process is not known. Following significant strides in the understanding of small non-coding RNA mediated gene regulation and PIWI-interacting RNAs (piRNA) and their roles in germline development, the function of Chromatoid Bodies (CB) has been somewhat elucidated. However, due to similarities with RNP granules found in somatic cells – such as stress granules and processing bodies – chromatoid body is thought to be involved in post-transcriptional regulation of gene expression. Postmeiotic germ cell differentiation induces the accumulation of piRNAs and proteins of piRNA machinery along with several distinct RNA regulator proteins. Although evidence suggests CB involvement in mRNA regulation and small RNA mediated gene regulation, the mechanism of action remains obscure.

Alberto Kornblihtt Argentine molecular biologist

Alberto Kornblihtt is an Argentine molecular biologist who specializes in alternative ribonucleic acids splicing. Kornblihtt is credited with being among the first to document how a single transcribed gene can generate multiple protein variants. Kornblihtt was elected as a Foreign Associate of the National Academy of Sciences of the United States in 2011 and received the Diamond Award for the most relevant scientist of Argentina of the decade, alongside physicist Juan Martin Maldacena, in 2013.

References

  1. "Dr. James Manley". columbia.edu. Retrieved 2014-04-18.
  2. Dr.James Manley (20 July 2017). "CURRICULUM VITAE" (PDF). Retrieved 20 July 2017.
  3. "James L. Manley". American Academy of Arts & Sciences. Retrieved 2022-02-18.