Richard Maraia and other members of the Section of Molecular and Cell Biology are interested in RNA metabolism with continued studies of the biogenesis, metabolism, genomics, and function of tRNAs. Efforts focus on their transcription termination and 3'-end formation by RNA polymerase (RNAP) III and the role of the oligo(U)-3'-OH end-stabilizing eukaryotic protein, La in their expression pathway. Another focus is on the tRNA isopentenyltransferase that creates the anticodon-loop modification, i6A37 and its role in health, disease, development and sensitivity to rapamycin, an anti-proliferative drug that simulates nutrition deficiency and to which certain pediatric cancers develop resistance. Anticodon modifications can increase the specific activity of a tRNA for decoding, more so for one codon of a synonymous pair than the other. This creates the opportunity to encode information in the redundancy component of the genetic code, referred to as secondary or auxiliary genetic information. Trying to decipher this additional layer of genetic information and how it is used during growth and development are challenging projects for investigation.

      For both of the very highly conserved tRNA isopentenyltransferase and La, the human proteins can readily complement the respective gene-deletion phenotypes in fission yeast, allowing facile structure-function analyses which in some cases includes post-translational modifications, that can then be extended to human cell culture or mice. We are interested in the fact that while both La and TRIT1 are essential for early embryonic development, La is essential for growth of embryonic stem cells whereas TRIT1 is dispensable. The Section also focuses on La-related protein-4 (LARP4) which binds to, stabilizes and promotes the translation of a subset of mRNAs involved in certain stress and signaling pathways. This Section uses genetics together with biochemistry, genome-wide profiling, a variety of high throughput deep sequencing approaches as well as cell and structural biology, in model systems that include yeast, mammalian cultured cells, and gene-altered mice.

Selected Publications

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