NYIT researcher receives NHGRI grant to unlock mysteries in RNA sequencing

Shenglong Zhang, Ph.D., associate professor of biological and chemical sciences in NYIT College of Arts and Sciences and principal investigator, and Wenjia Li, Ph.D., associate professor of computer science in NYIT College of Engineering and Computing Sciences and collaborator on the study, received $350,000 from the NIH – National Human Genome Research Institute to unlock mysteries in RNA sequencing.

LC (liquid chromatography)/MS (mass spectrometry)-Based Direct RNA Sequencing with Concomitant Capability to Sequence Multiple Base Modifications at Single-base Resolution

RNA nucleotide modifications have been linked to major diseases such as breast cancer, type-2 diabetes, and obesity. More than 40 RNA nucleotide modifications have recently been discovered in SARS-CoV-2, the virus that causes COVID-19. Due to the lack of methods that can sequence unknown RNA modifications, their identities and functions remain a mystery. Shenglong Zhang’s one-year study aims to reveal the identity and location of the different modifications in RNA of any type, including unknown modifications like in SARS-CoV-2 RNA, all in one study.

Despite that more than 170 RNA nucleotide modifications have been discovered so far, very few of them have been examined in detail because the methods currently available are limited. Typically, these RNA mapping methods are tailored only for a single type of known nucleotide modification and cannot indicate any unknown or other type of nucleotide modifications even if they co-exist in the same RNA molecule. These RNA modifications are undetectable by current high throughput sequencing technologies, which do not directly sequence RNAs themselves, but sequence their cDNAs (complementary DNA that is synthesized from the RNAs as a template) that only contain the four canonical deoxynucleotides found in a DNA molecule, adenine (A), cytosine (C), guanine (G), and thymine (T).

Zhang’s new sequencing technology would allow for the discovery of previously unknown and different modifications in one RNA molecule as well as support research on the causes and eventual treatments for diseases linked to these nucleotide modifications.

Previous studies have shown that mass spectrometry (MS)-based sequencing is feasible in direct sequencing RNA without using cDNAs.

“We can now focus on further development of our technology as a general platform to sequence any nucleotide modifications, together with their RNA sequence of any type, once and for all in one single study,” said Zhang. “This information could be critical in understanding the infection cycle of SARS-CoV-2 and may potentially offer clues for understanding how SARS-CoV-2 makes people sick as well as developing effective treatments during the current pandemic or possible future reappearances.”

This study, conducted in partnership with Columbia University and Cerno Bioscience, is a continuation of Zhang’s ongoing research on the development of direct RNA sequencing previously supported by Zhang’s R21 grant. In 2017, he and Li received a $568,000 grant from the NIH’s National Human Genome Research Institute to develop RNA sequencing methods that can be used to analyze RNA modifications in human, animal, and bacterial cells.

Source – New York Institute of Technology