EpiGenie would like to thank Valentina Ignatova for covering this great meeting for us and the team over at EMBL providing complimentary registration.
There are many meetings focusing on various classes of RNA or particular RNA modifications held in Europe, but one meeting bringing together both aspects has been missing. This niche was filled in with the first Epitranscriptome meeting that took place in EMBL Heidelberg (Germany) this April. Being rather small with slightly less then 200 attendees but very intense, “The Epitranscriptome” brought together leading researchers working on various aspects of RNA modifications.
The meeting was mainly focused on, but not limited to, three types of RNA modifications: 3’-tailing, editing, and covalent modifications. The secondary structure of RNA (such as a talk about G Quadruplex structures by Shankar Balasubramanian from University of Cambridge, UK) and pseudouridylation (discussed by Wendy Gilbert from MIT, USA, Chengqi YI from Peking University, China, and Schraga Schwartz from Weizmann Institute of Science, Israel), however, were not forgotten.
Tailing in the regulation of mRNAs and small noncoding RNAs
Narry Kim | Seoul National University, Seoul, South Korea
The first day of the conference culminated in a keynote talk by Narry Kim. She started with a brief introduction of the TAIL-seq method, originally reported by the Kim lab in Molecular Cell and an improved version was presented at the conference. In their initial study, powered by TAIL-seq, they measured poly(A) tail lengths transcriptome-wide along with identification of terminal tail nucleotides. Now the Kim lab has gone deeper into the investigation of the dynamics of poly(A) tail formation vs. deadenylation, a story that is currently in press.
The second part of the talk was devoted to oligo-uridylation of mRNA tails, that serves as a decay mark, and its implication in vertebrate development. In their original TAIL-seq paper the lab showed that some mRNAs have G as a terminal nucleotide on their tails. At the end of her talk Narry Kim presented their latest, unpublished, data unraveling the mechanism of G-tail formation on mRNA and its biological significance.
RNA methylation in gene expression regulation
Chuan He | University of Chicago, USA
Chuan He started the second day of the conference with a presentation on N6-Methyladenosine (m6A), which has been under intense investigation by his lab during the last few years, and presented some new data on m6A readers. Earlier this year the He lab characterized m1A as another widespread RNA modification that occurs on eukaryotic mRNAs and facilitates translation initiation.
Continuing these studies they have made further insights into the link between m1A and translation. Even though the meeting was focused on RNA modifications, Chuan He also reported the in vitro studies performed to overcome challenges in deciphering the function of m6A modification of DNA that his lab recently characterized in Chlamydomonas reinhardtii.
Stem cell function and sensitivity to cytotoxic stress is controlled by protein translation rates
Michaela Frye | University of Cambridge, UK
“Michaela Frye highlighted a role in translation for one more RNA modification, 5mC. Her lab showed that NSun2 methylates the majority of tRNAs at the variable loop protecting them from cleavage and accumulation of tRNA fragments that repress translation. Her work now revealed that this repressive translational mechanism plays a crucial role in mediating survival of skin tumor cells from cytotoxic stress. Without NSun2-mediated tRNA-methylation skin tumors fail to regenerate after exposure to chemotherapeutic drugs.”
RNAcompete-S: complex RBP binding models derived from a single-step in vitro selection
Tim Hughes | University of Toronto, Toronto, Canada
One session of the meeting was dedicated to RNA-binding proteins (RBPs). Among others Tim Hughes presented the RNAcompete-S method. Earlier his lab developed an in vitro method to identify the specificity of RBPs.
They incubated RBPs of interest with an excess of designed RNA molecules followed by a microarray hybridization of bound ones. Though this method allowed sequence specificity to be determined, it was not suitable for determination of the structural specificities of RBP–RNA interactions.
To overcome this limitation the Hughes lab added a computational pipeline to the original method utilizing so called Sequence and Structure Models (SSM). In the tests they performed this improved method could accurately predict structure and sequence specificities for known RBPs.
Expanding the set of snoRNAs and snoRNA targets
Mihaela Zavolan | Biozentrum of the University of Basel, Basel, Switzerland
Mihaela Zavolan started her talk by discussing alternative polyadenylation, one of the main research interests in her lab. They discovered a novel function in alternative polyadenylation for Heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNPC). This protein is known to largely affect RNA life-cycle via the recognition and binding of poly-U tracts in RNA in a N6-methyladenosine (m6A) dependent manner. This mechanism is known as an “m6A-switch”.
Now Mihaela Zavolan’s lab showed that hnRNPC regulates the production of alternative 3`-UTR isoforms. The second part of the talk focused on small nucleolar RNAs (snoRNAs). There are 2 classes of snoRNAs and Zavolan’s lab focuses on C/D box snoRNAs that guide 2`-O-Me to their target RNAs (mainly pre-rRNAs). With a new method for high-throughput identification of 2`-O-Me sites and sophisticated computational analysis they characterized snoRNA – target interactions in more details than had previously been possible. Particularly they showed that many orphan snoRNAs act redundantly on previously known targets. Moreover they speculate that many snoRNAs seem to interact with mRNAs without detectable 2`-O-Me marks, yet further experiments to characterize these interactions remain to be carried out.
With a great line-up of speakers, inspiring discussions, and poster sessions presenting the latest data generated in the field, the organizers laid a solid foundation for future meetings on “the Epitranscriptome”.