Protein Machines on RNA Genes

Some of the most important motor proteins in our cells are nanomechanical enzymes that remodel RNA molecules or use RNA binding to initiate cell signaling.  RNA helicases, translocases and surveillance proteins all play a vital role in the dynamic life of the cell.  We study the molecular basis for their function using a combination of enzymology, crystallography and solution biophysics.  Using these approaches, we recently solved the structure of the human antiviral surveillance protein RIG-I, and we have developed a mechanical model for its role in innate immunity.  We continue to study the mechanisms of helicase enzymes important in viral replication (such as HCV NS3), and in the remodeling of RNA tertiary structures (such as DEAD-box protein Mss116).

The structure of RIG-I and its ability to bind and differentiate different RNA molecules.

Relevant Publications

Direct tracking of reverse-transcriptase speed and template sensitivity: implications for sequencing and analysis of long RNA molecules
Li-Tao Guo, Sara Olson, Shivali Patel, Brenton R Graveley and Anna Marie Pyle
Nucleic Acids Res 2022 (50) : 6980-6989
A minimal RNA ligand for potent RIG-I activation in living mice
Melissa M. Linehan, Thayne H. Dickey, Emanuela S. Molinari, Megan E. Fitzgerald, Olga Potapova, Akiko Iwasaki and Anna Marie Pyle
Sci Adv. 2018 (4) : e1701854
Environmentally triggerable retinoic acid-inducible gene I agonists using synthetic polymer overhangs
Christian R Palmer, Max E Jacobson, Olga Fedorova, Anna Marie Pyle and John T. Wilson
Bioconjug. Chem. 2018 (29) : 742-747
Selective RNA targeting and regulated signaling by RIG-I is controlled by coordination of RNA and ATP binding
Megan E. Fitzgerald, David C. Rawling, Olga Potapova, Xiaoming Ren and Anna Marie Pyle
Nucleic Acids Res. 2017 (45) : 1442-1454
Establishing the role of ATP for the function of the RIG-I innate immune sensor
David Rawling, Megan Fitzgerald and Anna Marie Pyle
Elife 2015 (4) : E09391
The RIG-I ATPase core has evolved a functional requirement for alosteric stabilization by the pincer domain
David Rawling, Andrew Kohlway, Dahai Luo, Steve C. Ding and Anna Marie Pyle
Nucleic Acids Res. 2014 (42) : 11601-11611
Parts, assembly and operation of the RIG-I family of motors
David C. Rawling and Anna Marie Pyle
Curr Opin Struct Biol. 2014 (25) : 25-33
Dicer-related helicase 3 (DRH-3) forms an obligate dimer for recognizing 22G-RNA
Megan Fitzgerald, Adriana Vela and Anna Marie Pyle
Nucleic Acids Res. 2014 (42) : 19-30
Defining the functional determinants for RNA surveillance by RIG-I
Andrew Kohlway, Dahai Luo, David C. Rawling, Steve C. Ding and Anna Marie Pyle
EMBO Rep. 2013 (14) : 772-779
Duplex RNA activated ATPases (DRAs): Platforms for RNA sensing signaling and processing
Dahai Luo, Andrew Kohlway and Anna Marie Pyle
RNA Biol. 2013 (10) : 111-120
The thermodynamic basis for viral RNA detection by the RIG-I innate immune sensor
Adriana Vela, Olga Fedorova, Steve O. Ding and Anna Marie Pyle
J Biol Chem. 2012 (287) : 42564-42573
Visualizing the determinants of viral RNA recognition by innate immune sensor RIG-I
Dahai Luo, Andrew Kohlway, Adriana Vela and Anna Marie Pyle
Structure 2012 (20) : 1983-1988
Structural insights into RNA recognition by RIG-I
Dahai Luo, Steve C. Ding, Adriana Vela, Andrew Kohlway, Brett D. Lindenbach and Anna Marie Pyle
Cell 2011 (147) : 409-422
RNA helicases and remodeling proteins
Anna Marie Pyle
Curr Opin Chem Biol. 2011 (15) : 636-642