Sandra Wolin | |
---|---|
Born | Sandra Lynn Wolin |
Alma mater | Princeton University (BA) Yale University (MD, PhD) |
Scientific career | |
Fields | Microbiology, biomedical research |
Institutions | Yale School of Medicine National Cancer Institute |
Thesis | The Ro Small Cytoplasmic Ribonucleoproteins of Mammalian Cells (1985) |
Doctoral advisor | Joan A. Steitz |
Other academic advisors | Peter Walter |
Sandra Lynn Wolin is an American microbiologist and physician-scientist specialized in biogenesis, function, and turnover of non-coding RNA. She is chief of the RNA Biology Laboratory at the National Cancer Institute.
Wolin completed an A.B. in Biochemical Sciences from Princeton University. She earned a M.D. from the Yale School of Medicine and a Ph.D. degree from the department of molecular biophysics and biochemistry at Yale University. [1] Her 1985 dissertation was titled, The Ro Small Cytoplasmic Ribonucleoproteins of Mammalian Cells. Wolin's doctoral advisor was Joan A. Steitz. [2] She carried out postdoctoral training with Peter Walter at the University of California, San Francisco, where she devised an early ribosome profiling method. [1]
Wolin returned to the Yale School of Medicine as an assistant professor, and rose to the rank of professor in the departments of cell biology and molecular biophysics and biochemistry. From 2014-2017, she served as director of the Yale Center for RNA Science and Medicine. She joined the National Cancer Institute (NCI) in 2017 as chief of the newly formed RNA Biology Laboratory. She heads the section on non-coding RNAs and ribonucleoprotein particles (RNPs). [1]
Wolin's research examines how noncoding RNAs function, how cells recognize and degrade defective RNAs and how failure to degrade these RNAs affects cell function and contributes to human disease. [3] Wolin studies the biogenesis, function, and turnover of non-coding RNAs. Her laboratory has identified proteins that recognize misfolded and otherwise defective RNAs. By studying a bacterial ortholog of one such protein, the ring-shaped Ro60 autoantigen, they discovered that this protein is tethered by noncoding "Y RNA" to a ring-shaped nuclease, forming a double-ringed ribonucleoprotein machine specialized for structured RNA degradation. The laboratory is characterizing this new RNA degradation machine, identifying additional roles for Ro60 and Y RNA in both human cells and bacteria, and uncovering other pathways by which defective and damaged RNAs are recognized and degraded. [1]
Wollin is an elected fellow of the American Association for the Advancement of Science and American Academy of Microbiology. [4] [1]
The nucleolus is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signal recognition particles and plays a role in the cell's response to stress. Nucleoli are made of proteins, DNA and RNA, and form around specific chromosomal regions called nucleolar organizing regions. Malfunction of the Golgi apparatus means that nucleocid is the cause of several human conditions called "nucleolopathies" and the nucleolus is being investigated as a target for cancer chemotherapy.
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.
Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.
A non-coding RNA (ncRNA) is a functional 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.
The Max Planck Institute of Biochemistry is a research institute of the Max Planck Society located in Martinsried, a suburb of Munich. The institute was founded in 1973 by the merger of three formerly independent institutes: the Max Planck Institute of Biochemistry, the Max Planck Institute of Protein and Leather Research, and the Max Planck Institute of Cell Chemistry.
snRNPs, or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.
Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribed by either RNA polymerase II or RNA polymerase III. Their primary function is in the processing of pre-messenger RNA (hnRNA) in the nucleus. They have also been shown to aid in the regulation of transcription factors or RNA polymerase II, and maintaining the telomeres.
Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. It involves the coordinated function of over 200 proteins in the synthesis and processing of the three prokaryotic or four eukaryotic rRNAs, as well as assembly of those rRNAs with the ribosomal proteins. Most of the ribosomal proteins fall into various energy-consuming enzyme families including ATP-dependent RNA helicases, AAA-ATPases, GTPases, and kinases. About 60% of a cell's energy is spent on ribosome production and maintenance.
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.
Joan Elaine Argetsinger Steitz is Sterling Professor of Molecular Biophysics and Biochemistry at Yale University and Investigator at the Howard Hughes Medical Institute. She is known for her discoveries involving RNA, including ground-breaking insights into how ribosomes interact with messenger RNA by complementary base pairing and that introns are spliced by small nuclear ribonucleic proteins (snRNPs), which occur in eukaryotes. In September 2018, Steitz won the Lasker-Koshland Award for Special Achievement in Medical Science. The Lasker award is often referred to as the 'American Nobel' because 87 of the former recipients have gone on to win Nobel prizes.
Y RNAs are small non-coding RNAs. They are components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with systemic lupus erythematosus. They are also reported to be necessary for DNA replication through interactions with chromatin and initiation proteins. However, mouse embryonic stem cells lacking Y RNAs are viable and have normal cell cycles.
The 5S ribosomal RNA is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life, with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation coefficient in an ultracentrifuge, which is measured in Svedberg units (S).
Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.
60S ribosomal protein L22 is a protein that in humans is encoded by the RPL22 gene on Chromosome 1.
Thomas Arthur Steitz was an American biochemist, a Sterling Professor of Molecular Biophysics and Biochemistry at Yale University, and investigator at the Howard Hughes Medical Institute, best known for his pioneering work on the ribosome.
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.
HSURs are viral small regulatory RNAs. They are found in Herpesvirus saimiri which is responsible for aggressive T-cell leukemias in primates. They are nuclear RNAs which bind host proteins to form small nuclear ribonucleoproteins (snRNPs). The RNAs are 114–143 nucleotides in length and the HSUR family has been subdivided into HSURs numbered 1 to 7. The function of HSURs has not yet been identified; they do not affect transcription so are thought to act post-transcriptionally, potentially influencing the stability of host mRNAs.
Anti-SSA autoantibodies are a type of anti-nuclear autoantibodies that are associated with many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus and primary biliary cirrhosis. They are often present in Sjögren's syndrome (SS). Additionally, Anti-Ro/SSA can be found in other autoimmune diseases such as systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), and are also associated with heart arrhythmia.
Messenger RNP is mRNA with bound proteins. mRNA does not exist "naked" in vivo but is always bound by various proteins while being synthesized, spliced, exported, and translated in the cytoplasm.
Susan J. Baserga is an American physician who is the William H. Fleming Professor of Molecular Biophysics and Biochemistry at Yale University. Her research considers the molecular basis of ribosomes, and the mechanistic basis of inherited human disease.