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"Junk" RNA Regulates Important Cellular Processes

Researchers discover a connection between noncoding RNA and the silencing of genes

No. 34 | 08/05/2006 | by (Jow)

It has been known for a long time that much of a cell’s RNA stems from DNA regions called intergenic spacers (IGS) that lie between two genes and do not code for proteins. A research group headed by Professor Ingrid Grummt of the Division "Molecular Biology of the Cell II"” at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) has now discovered the important role of noncoding RNA molecules originating from IGS regions in a number of control processes including the regulation of ribosomal RNA (rRNA) production. The scientists have published their results in the latest issue of the journal Molecular Cell*.

RNA, another type of nucleic acid alongside DNA, is an important carrier of genetic information on the way from gene to protein. Alongside this 'messenger' RNA, or mRNA, there are numerous other types of RNA that are very important for the cell. The article deals with a further type of RNA of which the DKFZ researchers have discovered a new function.

This discovery is only the tip of the iceberg. "About 95 percent of cellular DNA is noncoding, i.e. contains no information for protein synthesis. Transcripts of these noncoding gene segments, however, are chief regulators of gene activity within the cell and it is likely that they are even more relevant than proteins," explains Dr. Christine Mayer. The biological value of these results is tremendous: For the first time ever, researchers have come across a mechanism that shows how transcripts that have so far been neglected as "junk" RNA play an active role in regulation processes at the chromatin level. Scientists have known for some time about the existence of this seemingly functionless RNA. What is new is the realization that these molecules are of essential relevance for the cell. The long-held assumption that key regulation processes are controlled only by proteins is no longer valid in this form. "We may even dare to maintain that proteins are presumably responsible only for the basic structure and function of the cell, while RNA is used for its regulation," says Mayer. Hence, RNA molecules are a central part of cellular regulation processes and more important than previously thought.

The genes from which ribosomal RNA is read are separated by noncoding IGS sequences. The researchers have shown that these IGS sequences are transcribed and the transcripts play an important role in the regulation of its surrounding gene sequences. DNA is found in the cell in the form of chromatin. If it is to be read, special chromatin-modifying protein complexes have to unpack the genetic material to make it accessible for the transcription machine. These complexes are also able to pack DNA in such a way that reading is no longer possible.

Such a function is performed by the nucleolar remodeling complex NoRC. The NoRC complex is capable of switching off those parts of the DNA from which rRNA is read. Grummt’s team showed that NoRC can only silence rRNA genes if an RNA component is bound to the protein complex. This NoRC-associated RNA component is an intergenic transcript, i.e. those RNAs that are read from the noncoding regions located between the rRNA genes. This means that those small RNA molecules that were previously regarded as "junk" without special function are able to remodel the chromatin structure and, thus, to switch off the gene activity of the rDNA locus.

* Christine Mayer, Kerstin-Maike Schmitz, Junwei Li, Ingrid Grummt, Raffaella Santoro: Intergenic Transcripts Regulate the Epigenetic State of rRNA Genes. Molecular Cell, Vol 22, 351-361

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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