Structure and Function of Large RNAs

Many cellular processes are catalyzed and regulated by large, highly structured noncoding RNA molecules. Our laboratory is interested in the tertiary structures of large RNA molecules that control RNA splicing, transcription, and viral pathogenicity. We use a combination of biochemistry, cell biology and crystallography to monitor the architectural states of large RNAs and to understand the link between their molecular structure and function in biology. We recently solved the structure of a self-splicing group II intron (one of the largest ribozymes in nature), and we are now using similar techniques to determine the tertiary structure of lincRNAs, viral RNAs, and other RNAs that play a central role in gene expression.

Structure and RNA folding kinetics of group II introns.

Relevant Publications

MRT-ModSeq–Rapid detection of RNA modifications with MarathonRT Rafael de Cesaris Araujo Tavares, Gandhar Mahadeshwar, Han Wan, Anna Marie Pyle bioRxiv 2023 () :
Making RNA: Using T7 RNA polymerase to produce high yields of RNA from DNA templates Tianshuo Liu, Shivali Patel, Anna Marie Pyle Methods in Enzymology 2023 () :
Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq Shivali Patel, Alec N Sexton, Madison S Strine, Craig B Wilen, Matthew D Simon, Anna Marie Pyle Nature Communications 2023 (14) : 3426
Structures of a mobile intron retroelement poised to attack its structured DNA target Kevin Chung, Ling Xu, Pengxin Chai, Junhui Peng, Swapnil C Devarkar, Anna Marie Pyle Science 2022 (378) : 627-634
A molecular beacon assay for monitoring RNA splicing Qusay Q Omran, Olga Fedorova, Tianshuo Liu, Anna M Pyle Nucleic Acids Res 2022 (50) : e74
An ultra-processive, accurate reverse transcriptase encoded by a metazoan group II intron Chen Zhao, Fei Liu and Anna Marie Pyle RNA 2018 (24) : 183-195
The SMAD3 transcription factor binds complex RNA structures with high affinity Thayne Dickey and Anna Marie Pyle Nucleic Acids Res. 2017 (45) : 11980-11988
The group II intron maturase: a reverse transcriptase and splicing factor go hand in hand Chen Zhao and Anna Marie Pyle Curr Opin Struct Biol. 2017 (47) : 30-39
Visualizing the secondary and tertiary architectural domains of lncRNA RepA Fei Liu, Srinivas Somarowthu and Anna Marie Pyle Nat Chem Biol 2017 (13) : 282-289
Inverted repeat Alu elements in the human lincRNA-p21 adopt a conserved secondary structure that regulates RNA function Isabel Chillon and Anna Marie Pyle Nucleic Acids Res. 2016 (44) : 9462-9471
Crystal structure of group II intron domain 1 reveals a template for RNA assembly Chen Zhao, K.R. Rajashankar, Marco Marcia and Anna Marie Pyle Nature Chemical Biology 2015 (11) : 967-972
Native Purification and Analysis of Long RNAs Isabel Chillón Gazquez, Marco Marcia, Michal Legiewicz, Fei Liu, Srinivas Somarowthu and Anna Marie Pyle Methods in Enzymology 2015 (558) : 3-37
HOTAIR forms an intricate and modular secondary structure Srinivas Somarowthu, Michal Legiewicz, Isabel Chillón Gazquez, Marco Marcia, Fei Liu and Anna Marie Pyle Mol Cell 2015 (58) : 353-361
Rediscovering RNA Anna Marie Pyle RNA 2015 (21) : 714-715
Principles of ion recognition in RNA: insights from the group II intron structures Marco Marcia and Anna Marie Pyle RNA 2014 (20) : 516-27
Visualizing the ai5γ group IIB intron Srinivas Somarowthu, Michal Legiewicz, Kevin S. Keating and Anna Marie Pyle Nucleic Acids Res. 2013 (42) : 1947-58
Visualizing group II intron catalysis through the stages of splicing Marco Marcia and Anna Marie Pyle Cell 2012 (151) : 497-507
The brace for a growing scaffold: Mss116 protein promotes RNA folding by stabilizing an early assembly intermediate Olga Fedorova and Anna Marie Pyle J Mol Biol. 2012 (422) : 347-365
The molecular interactions that stabilize RNA tertiary structure: RNA motifs, patterns, and networks Samuel E. Butcher, Anna Marie Pyle Acc Chem Res. 2011 (44) : 1302-1311