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Non-Protein Coding RNA
17-19 March
Marseille, France
Organisers:
Juergen Brosius: University of Muenster, Germany
Carole Charlier: University of Liege, Belgium
Gerhart Wagner: University of Uppsala, Sweden
Renee Schroeder: University of Vienna, Austria
Herve Vaucheret: INRA, Versailles, France
Witold Filipowicz : Friedrich Miescher Institute, Basel, Switzerland
Eric Wiemer: University of Rotterdam, Netherlands
Martin Crespi: CNRS, France
Report
Summary
The dark ages for non-protein-coding RNAs (npcRNAs) are over. These macromolecules not only constitute important players in gene and genome evolution but also are vital for a astounding variety of cellular functions and key regulatory pathways in modern organisms.
During all periods including the recent soaring of the field, European scientists have made important contributions. This meeting brought established scientists that participated in several EU sponsored RNA-based STREPs together and, importantly, also admixed junior scientists including graduate students. About sixty participants from all corners (~15 European plus 2 Near-Eastern countries) exchanged their findings on various aspects of RNA Biology, from large npcRNAs to the tiniest (miRNAs), from systems as diverse as plants, fungi, invertebrates, vertebrates including mammals, bacteria, in normal development and cellular function as well as disease using computational and wet-lab approaches. Several posters were presented and accessible for discussion during the entire meeting. The pleasant setting at the Mediterranean coast in Carry-Le-Rouet near Marseille and secluded location lead to vivid and prolonged discussion among all participants. It is certain that all participants greatly benefited from these exciting interactions in an exploding field. Scientific
Content
Only a few years ago, the pervasive role of non-protein-coding RNA (npcRNA), in cellular function and genome evolution was unimaginable. Today, however, a combination of biocomputational and experimental methods indicates that mammalian genomes harbour a great number of highly diverse npcRNAs. Among them are more than one thousand micro RNAs (miRNAs) alone. These short RNAs (~20-25 nucleotides, nt) play key roles in regulation of gene expression at important stages in organismal development. Furthermore, hundreds of novel snoRNAs have been discovered. The potential complexity of large mRNA-like RNAs that do not encode protein (some may encode peptide) is stunning. It needs to be established, however, how many of these RNAs are mere transcriptional noise. Apart from complementing our understanding of gene regulation and the fact that npcRNA have –just like proteins - the potential to be involved in the etiology of human disease, a lot of hope rests on miRNAs and short interfering RNAs (siRNAs) as future tools for diagnostics and therapeutic intervention in a number of diseases including cancer.
The scientific content of the meeting was divided into five parts, reflected in five sessions :
I. npcRNAs in development
II. Small RNAs in silencing and gene regulation
III. npcRNAs in Epigenetics
IV. npcRNA regulation in Prokaryotes
V. npcRNAs in Biomedicine
Part I, npcRNAs in development consisted of a general introduction, history and overview entitled “Experimental RNomics: from fishing to function” to riboregulator function with respect to plant SINE RNAs. Continuing in plants the next topics were “overexpression of three novel riboregulators that affects plant differentiation” as well as integration of plastochron and flowering control by microRNAs and “Riboregulation in the phosphate starvation rescue system of Arabidopsis” and “Integration of plastochron and flowering control by microRNAs” and “Riboregulation in the phosphate starvation rescue system of Arabidopsis”. The subject then switched to “MicroRNAs as targets for antisense-based therapeutics”, “an Alu-derived intronic splicing enhancer element affects aberrant pre mRNA processing in ATM” and ended with a presentation on the “interplay between HSF1 and HSF2 in the Nuclear Stress Bodies”.
Part II, small RNAs in silencing and gene regulation began with the exciting story about the unexpected role of a miRNA in farm animal husbandry “From sheep to human: Polymorphic miRNA-target interactions, a common mediator of phenotypic variation ?” and continued with the description of “new subclasses of small RNAs in C. elegans and zebrafish". Turning to plants, we heard about “virus induced RNA silencing and suppression interplay between plant viruses and host defence”, “genetic dissection of small RNA pathways in Arabidopsis”, “Virp1, a host factor necessary for the infectivity of PSTVd in Nicotiana benthamiana and Nicotiana tabacum plants”, “analysis of Arabidopsis thaliana small RNAs by tiling microarray hybridization” and eventually about “small RNAs in Dictyostelium discoideum”, a small social amoeba.
In part III, npcRNAs in Epigenetics we learned about “ tracking imprinted non-protein-coding RNAs at the single nucleus level”, “large and small imprinted non-coding RNAs at the Dlk1-Dio3 imprinted domain on mouse chromosome 12” and the amazing story of “RNA mediated heredity of an epigenetic trait in the mouse”. Leaving vertebrates we learned about “epigenetic programming of genome rearrangements in ciliates: A natural genomic subtraction mediated by RNA interference”.
Part IV, npcRNA regulation in Prokaryotes, ranged in topics from “a multi-functional RNA coordinately regulates the expression of several virulence factors in Staphylococcus aureus” and “Hfq-binding RNAs of E. coli” to “regulatory RNAs in bacterial stress response regulation” and “identification of new non-protein-coding RNAs in Listeria monocytogenes and prediction of mRNA targets”
Part V, npcRNAs in biomedicine began with “regulation of neuronal plasticity by microRNAs”, switching to the role of “miRNAs and cancer”, and the observation that “induction of microRNA-21contributes to the oncogenic potential of Stat3” to the “use of artificial micro RNA (amiRNAs) for gene silencing of three full aquaporins subfamilies from Arabidopsis thaliana”.
Posters were also presented representing a broad range of RNA-related subjects ranging from bacterial tmRNA, a hybrid between a tRNA and mRNA, brain-specific snoRNAs, vault RNAs, RNA-binding proteins, such as La, Hfq, DRB1, RNA silencing via ABCG2 transporter, miRNA and other npcRNA arrays, miRNA profiles, miRNAs in heat shock, transcription factor regulation by miRNAs, high-throughput npcRNA sequencing, computational approaches to npcRNA identification and characterization, as well as miRNA target prediction.
There was plenty of time for questions and discussion. This activity was vividly extended into to lunch and dinner, where participants sat at several large tables and thus mixed and mingled from different labs from Professor to student. The poster sessions were very well attended and also provided a great opportunity for scientific exchange.
Assessment of the results & impact of the event
This 3-day workshop focusing on npcRNA (tiny, small, and large) from organisms ranging from multicellular Eukarya (plants, animals) and single cellular Eukarya to Bacteria and Archaea was considered by participants and organizers alike as a great success and all went home with more knowledge about npcRNAs after freely and intensively discussing the exciting aspects of their predictions, discoveries, validation, function and biological diversity. Many collaborations were extended or initialized.
A second goal, to bring participants of the RIBOREG STREPand thematically related STREPs, including “FOSRAK”, “BACRNA”, “Callimir” as well as other European scientists working on npcRNAs together in joint grant applications came – at least up to now and on a larger scale – not to fruition. Perhaps we have to await additional calls of FP7 to integrate more partners between the previous STREPs. Programme
Saturday March 17 :
14:00 -14:50 Registration
14:50 Welcome (J. Brosius)
15:00 – 18:30 npcRNAs in development
Chairman: M. Crespi
15:00 – 15:30 J. Brosius : “Experimental RNomics: from fishing to function”
15:30 – 16:00 J. M. Deragon : “A riboregulator function for plant SINE RNAs”
16:00 – 16:15 M. Crespi : “Overexpression of three novel riboregulators affects plant differentiation”
16:15 – 16:30 Coffee break
16:30 – 17:00 S. Kauppinen : “MicroRNAs as targets for antisense-based therapeutics”
17:00 – 17:30 J. W. Wang : “Integration of plastochron and flowering control by microRNAs”
17:30 – 17:45 J. Paz Ares : “Riboregulation in the phosphate starvation rescue system of Arabidopsis”
17:45 – 18:00 SOP: F. Pagani : “An Alu-derived intronic splicing enhancer element affects aberrant pre mRNA processing in ATM”
18:00 – 18:15 SOP: A. Sandqvist : “Interplay between HSF1 and HSF2 in the Nuclear Stress Bodies”
18:15 – 18:30 Coffee break
18:30 – 20:00 poster session and discussions
20:00 – 21:00 dinner
March 18 :
8:00 – 9:00 breakfast
9:00 – 12:45 Small RNAs in silencing and gene regulation
Chairman: H. Vaucheret
9:00 – 9:30 C. Charlier : “From sheep to human: Polymorphic miRNA-target interactions, a common mediator of phenotypic variation ?”
9:30 – 10:00 J. van Wolfswinkel : “"New subclasses of small RNAs in C. elegans and zebrafish"
10:00 – 10:30 J. Burgyan “Virus induced RNA silencing and suppression Interplay between plant viruses and host defence”
10:30 – 10:45 coffee break
10:45 – 11:15 H. Vaucheret : “Genetic dissection of small RNA pathways in Arabidopsis”
11:15 – 11:45 F. Söderbom : “Small RNAs in Dictyostelium discoideum”
11:45 – 12:15 K. Kalantidis : “Virp1, a host factor necessary for the infectivity of PSTVd in Nicotiana benthamiana and Nicotiana tabacum plants”
12:15 – 12:30 SOP: M. Boccara : “Analysis of Arabidopsis thaliana small RNAs by tiling microarray hybridization”
12:30 – 12:45 SOP: S. Hennig : “Experimental validation of predicted non-protein-coding RNAs”
12:45 – 14:30 lunch break
14:30 – 16:45 npcRNAs in Epigenetics
Chairman: J. M. Deragon
14:30 – 15:00 J. Cavaillé : “Tracking imprinted non-protein-coding RNAs at the single nucleus level”
15:00 – 15:30 A. Ferguson-Smith : “Large and small imprinted non- coding RNAs at the Dlk1-Dio3 imprinted domain on mouse chromosome 12”
15:30 – 16:00 M. Rassoulzadegan : “RNA mediated heredity of an epigenetic trait in the mouse”
16:00 – 16:30 E. Meyer : “Epigenetic programming of genome rearrangements in ciliates: A natural genomic subtraction mediated by RNA interference”
16:30 – 16:45 SOP: A. Slonimsky : “Sequence structure identification and characterization of C6orf217: A positional candidate for schizophrenia”
16:45 - 17:00 Coffee break
17:00 – 19:00 npcRNA regulation in Prokaryotes
Chairman: J. Brosius
17:00 – 17:30 P. Romby : “A multi-functional RNA coordinately regulates the expression of several virulence factors in Staphylococcus aureus”
17:30 – 18:00 R. Schroeder : “Hfq-binding RNAs of E. coli”
18:00 – 18:30 G. Wagner : “Regulatory RNAs in bacterial stress response regulation”
18:30 – 19:00 F. Repoila : “Identification of new non-protein-coding RNAs in Listeriamonocytogenes and prediction of mRNA targets”
19:00 – 20:30 poster session and discussions
20:30 – 21:30 dinner
March 19:
8:00 – 9:00 breakfast
9:00 – 12:00 npcRNAs in Biomedicine
Chairman: E. Wiemer
9:00 – 9:30 G. Obernosterer : “Regulation of Neuronal Plasticity by microRNAs”
9:30 – 10:00 E. Wiemer “miRNAs and Cancer”
10:00 – 10:15 SOP: N. Sade : The use of Artificial Micro RNA (amiRNAs) for gene silencing of three full aquaporins sub families from Arbidopsis thaliana”
10:15 – 10:30 SOP: A. Kretzschmar : “Induction of microRNA-21 contributes to the oncogenic potential of Stat3”
10:30 – 10:45 Coffee break
10:45 – 12:00 General Discussion, FP7, Integration of EEC Projects
12:00 – 14:00 lunch
End of workshop
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