BME Special Seminar: La protein and the RNA Polymerase III transcriptome

Presenter: Richard J Maraia, MD, Senior Investigator and Head of the Section on Molecular and Cell Biology in the Intramural Research Program, NICHD

Description: The La protein is a eukaryote-ubiquitous RNA-binding protein that (in the organisms examined) stabilizes newly synthesized RNA polymerase (Pol) III transcripts by transiently protecting their 3’-ends prior to maturation as abundant stable noncoding (nc)RNAs. While Bacteria and archaea use a single RNA polymerase to produce their cellular RNAs, Pol III is specialized to synthesize short RNAs in large amounts, e.g., tRNAs at >10-fold molar levels relative to ribosomal RNA synthesized by Pol I. tRNA genes are the most numerous of Pol III-transcribed genes, followed by 5S rRNA and a few single-to-low copy noncoding (nc)RNA genes. The numbers of tRNA genes have been expansive and dynamic in eukaryotes, presumably facilitated by their “internal split promoter” (A-box and B-box) which roughly correspond to the most conserved regions of tRNAs, the D and T loops. The Pol III-specific transcription factor, TFIIIC binds to this promoter and directs transcription at the upstream initiation site, i.e., even if the tRNA sequence is inserted at a different locus. Transcription termination by Pol III is by a unique mechanism, directed by its second largest subunit, RPC2 which together with help of another Pol III-specific subunit reads the ≥4 consecutive Ts on the nontemplate strand as a pause signal that results in release the RNA. The first part of the talk will be on a paper under revision, A POLR3B-variant reveals a RNA Polymerase III transcriptome response dependent on the SSB/La protein. In this study, we performed extensive molecular characterization on a patient case that we found in the NIH Undiagnosed Disease Program (UDP) with homozygous SNPs in RPC2 and gained new insight as per the title. The second part of the talk will be related to a paper published in July 2025 that reflects diversity of tRNA genes. More specifically, we discovered a tRNA gene with apparent latent noncanonical activity to activate cellular interferon signaling, in addition to its mRNA decoding activity, and characterized its features and those of a minority subset of other human tRNA genes that exhibit this activity from those in a majority that don’t.

Bio: Richard J. Maraia focuses on RNA polymerase III, Genetics, RNA, Small nuclear RNA and RNA polymerase II. The study incorporates disciplines such as Inverted repeat, Genomic organization, Termination factor, Molecular biology and Heterochromatin in addition to RNA polymerase III. His Molecular biology research incorporates elements of Apoptosis, Mdm2, Cancer research and Small interfering RNA.

His studies in RNA integrate themes in fields like Transcription and Protein biosynthesis. The concepts of his Small nuclear RNA study are interwoven with issues in RNase P and RNA recognition motif. Richard J. Maraia has included themes like General transcription factor and DNA polymerase in his RNA polymerase II study.

He is the ongoing chair of the NIH RNA club and serves on the organizing committees of the international biennial conferences on RNA polymerases I & III and the biennial conferences on La and related protein (LARP). He served on the Earl Stadtman Investigator Search committees for Molecular Biology and Biochemistry as chair and for RNA Biology at the NIH. He had speciality training in pediatrics and interinstitute medical genetics at the NIH.

Hosted by: Professor Todd Lowe, BME Department