Richard J. Maraia, M.D.
Section on Molecular and Cell Biology
RNA Metabolism in Cell Biology, Growth, and Development
We are interested in how the biogenesis and metabolism pathways for small RNAs, especially tRNAs and mRNAs, interact with pathways that control cell proliferation, growth, and development. We focus on RNA polymerase (Pol) III and the post-transcriptional handling of its transcripts by the RNA-binding protein La, which, together with La-related protein-4 (LARP4), contributes to translational control and the cell’s growth capacity. In addition to its major products (tRNAs and 5S rRNA), Pol III synthesizes other non-coding RNAs. Tumor suppressors and oncogenes mediate deregulation of Pol III transcript production, contributing to increased capacity for proliferation of cancer cells. The La protein is a target of autoantibodies prevalent in (and diagnostic of) patients with Sjögren’s syndrome, systemic lupus, and neonatal lupus. La contains several nucleic acid–binding motifs as well as several subcellular trafficking signals and associates with non-coding and messenger RNAs to coordinate activities in the nucleus and cytoplasm. The La protein functions by protecting its small RNA ligands from exonucleolytic decay. Our recent studies showed that human LARP4 protects certain mRNAs from decay, in a polyribosome-associated manner. We strive to understand the structure-function relationship and cell biology of La’s and LARP4’s contribution to growth and development. We use genetics, cell and structural biology, and biochemistry in model systems that include yeast, human tissue culture cells, and gene-altered mice.
A major interest is in deciphering what we refer to as "secondary information" in the genetic code. This information derives from the choice use of synonymous codons that encode the same amino acid. This can produce a layer of information beyond that which provides the amino acid sequence of a protein. That is to say that in addition to providing the template for the sequence of a protein, the use of certain synonymous codons can also produce additional biochemical effects, which we refer to as 'secondary information." The effects can be related to ribosome pausing which can affect protein folding, or alteratons of the stability of the mRNA. Other types of secondary information can also be encoded in the choice use of synonymous codons, for example sets of mRNAs that share similar patters of synonymous codon bias are similarly sensitive to tRNAs with the same anticodon modification and exhibit similar patterns of efficiency of translation elongation. The components of the secondary information system are the tRNA pool, the tRNA modification enzymes, and the codon bias distribution among the mRNAs.
Dr. Richard Maraia is a Senior Investigator and Head of the Section on Molecular and Cell Biology in the Intramural Research Program of the NICHD. Dr. Maraia directs a basic research program in Molecular Genetics and Genomics that seeks to understand the influences of genetics, biochemistry, and cell biology on the programmed metabolism of small nuclear RNAs and messenger RNAs, and how this contributes to growth and development. Of molecular interest is the structural plasticity of the human La antigen and related proteins in their ability to accommodate specific binding to a variety of RNAs that differ in sequence and structure. A major interest is in the biogenesis and metabolism of transfer RNAs, the genetic adapters that translate the genetic code, and the influences of their dynamics and relative abundances on codon bias-driven genetic programs involved in normal growth and in response to the physiologic states of stress and disease.
Dr. Maraia received an Associate of Science degree from Kingsborough Community College (KCC) of the City University of New York. He was awarded The KCC Dean's Scholarship to Columbia University from which he received a B.S. in Biological Sciences. Maraia received his M.D. from Cornell University Medical College. He obtained specialty training as an Intern and Resident in Pediatrics at The New York Hospital. Dr. Maraia then went to the NICHD as a Clinical Fellow and also trained in the Interinstitute Medical Genetics Program of the NIH. Dr. Maraia's service includes ongoing Chairmanship of the NIH Regional RNA Club. He also regularly serves on the Organizing Committees of the International Biennial Conferences on RNA Polymerases I & III, the Biennial Conferences on La and Related Protein (LARP). He has also served on the Earl Stadtman Investigator Search Committees for Molecular Bioilogy and Biochemistry (as Chair) and for RNA Biology at the NIH.
Arimbasseri AG, Kassavetis GA, Maraia RJ. Transcription. Comment on "Mechanism of eukaryotic RNA polymerase III transcription termination". Science. 2014;345(6196):524.
Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E, Bruni F, Donnini C, Vassilev A, He L, Blakely EL, Griffin H, Santibanez-Koref M, Bindoff LA, Ferrero I, Chinnery PF, McFarland R, Maraia RJ, Taylor RW. Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA. PLoS Genet. 2014;10(6):e1004424.
Rijal K, Maraia RJ. Active Center Control of Termination by RNA Polymerase III and tRNA Gene Transcription Levels In Vivo. PLoS Genet. 2016;12(8):e1006253.
Mattijssen S, Arimbasseri AG, Iben JR, Gaidamakov S, Lee J, Hafner M, Maraia RJ. <i>LARP4</i> mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection. Elife. 2017;6.
Arimbasseri AG, Maraia RJ. Mechanism of Transcription Termination by RNA Polymerase III Utilizes a Non-template Strand Sequence-Specific Signal Element. Mol Cell. 2015;58(6):1124-32.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on July 26th, 2018