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The discovery described in the pages of Nature emerges from a study conducted by Fabrizio d'Adda di Fagagna atIFOM in Milan, in collaboration with the CNR in Pavia, the IIT atthe IFOM-IEO in Milan and the Riken Omics Science Center inYokohama, Japan. Given the importance of the cellular DNA damage response in aging,in the repression and control of tumour development, and intherapeutic treatments for cancer, the discovery could openpromising interpretive and potentially therapeutic perspectives. For decades the scientific community has attributed a role to RNAthat is subordinate to that of DNA: the functional processes ofexpression of genetic information into proteins. With some knownexceptions, such as the classes of tRNA and rRNA involved in thesynthesis of proteins, RNA molecules were considered"fleeting" messengers necessary to carry geneticinstructions from the nucleus, site of the genome, to the cytoplasmwhere proteins, the scaffolding of living organisms, are produced. In recent years, this simplistic view has given way to anincreasingly complex scenario, with the identification of new RNAclasses involved in numerous cellular events. One in particular, however, had never been identified or describedto date: it is DDRNA, a class of non protein-coding RNAs that aregenerated every time the genome is damaged. They originate from thesame sequence of DNA damaged and have the essential task oflaunching the molecular alarms through which the cell detects theproblem and resolves it by repairing the damage. Therefore, the integrity of the genome depends on DDRNA. The discovery emerges from a study published online May 23 in thejournal Nature and coordinated by Fabrizio d'Adda di Fagagna, head of the"Telomeres and senescence" research program at IFOM (FIRCInstitute of Molecular Oncology) in Milan and a researcher at theCNR in Pavia. DDRNA (DNA Damage Response RNAs), were named precisely for theirability to trigger the cellular DNA damage response and are notsimply a new class of RNA that is added to other previously found. "All of the RNAs described so far -- says d'Adda di Fagagna --although very different in structure, sequence and mechanism ofaction, have essentially one thing in common: all contribute, atmultiple levels, to regulate the functional organization andexpression of the genome. The DDRNA are unique because theysafeguard genome integrity. For an RNA, it is a novel task thatbroadens the spectrum of the functional versatility so far provenfor this type of molecules." Therefore, this discovery represents a milestone in the processleading to a significant change in perspective for this area ofmolecular biology. Certainly new sequencing technologies are contributing torevolutionise the field by unravelling first the genomes ofnumerous plant and animal species, and then the so-calledtranscriptome -- the entire and specific program of RNA expressedby a cell. The DDRNA described today in Nature was identifiedthanks to the use of advanced genomic technologies, capable ofidentifying small amounts of RNA, by scientists at IFOM in closecollaboration with the team of Piero Carninci of the RIKEN OmicsScience Center at the RIKEN Yokohama Institute in Japan. Experiments were conducted at laboratories in Milan and Yokohamathat recreated stress conditions capable of generating DNA damagein cultured cells and then the complete set of RNA expressed fromthe damaged cells was sequenced. "The results of these analyzes have clearly demonstrated --Carninci comments -- that under such circumstances, short RNAmolecules are transcribed from the sequence of damaged DNA. Thisstudy has very important implications regarding the function of thenon-coding RNAs. These RNAs are often considered "genomicrubbish," because in many cases their function is not yetentirely clear. This study demonstrates unequivocally that evenshort RNA transcripts may play a role in maintaining genomeintegrity." Further investigations conducted at the IFOM haverevealed that cells rely on them to trigger the alarms necessaryfor the repair of their damaged genomes. DDRNA: a barrier against tumour development The DNA Damage Response or DDR is the reaction that a cell triggersto maintain its genomic integrity: when a DNA break is detected,the growth and proliferation of damaged cells are temporarilyhalted, thus avoiding conditions that cause genome rearrangementsand mutations that might predispose to cancer or the accumulationof irreparable DNA damage and cause cellular aging. Therefore, this system constitutes a very effective barrier to theuncontrolled cell growth that is typical of tumours. The experimental journey that led the team of d'Adda di Fagagna atIFOM, composed of Sofia France and Flavia Michelini, to thediscovery of DDRNA was inspired by the study of cancer cells:"Analysing these cells -- explains Sofia France, first authorof this study supported also by the Italian Institute of Technologyat the IFOM-IEO Campus in Milan -- we realized that when we blockedthe production of a specific class of non- coding RNAs, inside thecell nucleus the molecular alarms that signal the presence of DNAdamage were extinguished and the DDR mechanism was not activated;consequently, the tumour cells began to proliferate again." While pursuing research on this never before seen phenomenon, thescientists at IFOM have identified a novel role for RNA as amediator of the cellular response to DNA damage and, as such, as asuppressor of tumour growth. And not only: the accumulation of DNAdamage and persistent activation of the DDR are also associatedwith cellular senescence and organism aging, processes in whichthis new class of RNA may play a key role. Senescence and malignant transformation are in many ways oppositefaces of the same coin. For years, d'Adda di Fagagna and his teamhave been dedicated to studying these two closely linked cellularprocesses and their association with impaired genome integrity.Today's discovery reveals another piece of the puzzle that emergesfrom research conducted by the scientists at IFOM: "This newclass of RNA opens a completely new perspective for interpretingthe processes of aging and mechanisms of transformation and oftumour progression linked to the generation of DNA damage"says d'Adda di Fagagna. "In particular, we will nowinvestigate if the mechanisms of synthesis of these DDRNAs arealtered in cancer and the impact that these changes may have on theonset and development of tumours. It is in this direction --continues the scientist -- that we will continue our research in aclose collaboration between IFOM and the CNR of Pavia, where wehave recently established a laboratory dedicated to studying themaintenance of genomic stability." This work was realized with support from, among others, the FIRC(Italian Foundation for Cancer Research), AIRC (Italian Associationfor Cancer Research), the Human Frontier Science Program andTelethon. We are high quality suppliers, our products such as Smartphone Protective Case , Ipad 2 Protective Cases for oversee buyer. To know more, please visits Ipad 2 Protective Cases.
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