scienceblogs, Nobel a 2 donne

Evviva, domani verrà assegnato il Nobel per la Medicina a 2 donne della scienza, per la scoperta dei telomeri e del meccanismo di riparazione delle estremità del DNA importante durante l'invecchiamento cellulare.

Anche se questo riconoscimento arriva due decenni in ritardo, questo macchina anti-invecchiamento ancora riserva sorprese. L'enzima che riproduce queste sequenze di DNA, la telomerasi, agendo in associazione a delle sequenze di RNA telomerico, ora si è scoperto ha una nuova funzione, quella di sintetizzare RNA, una funzione che si riteneva fosse presente solo nelle piante.

Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere homeostasis. However, accumulating evidence suggests that the human telomerase reverse transcriptase catalytic subunit (TERT) contributes to cell physiology independently of its ability to elongate telomeres. Here we show that TERT interacts with the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a gene that is mutated in the inherited pleiotropic syndrome cartilage-hair hypoplasia. Human TERT and RMRP form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNA in a Dicer (also known as DICER1)-dependent manner. These observations identify a mammalian RdRP composed of TERT in complex with RMRP (Maida et al., Nature, 2009, 461:230-5).

E' un capitolo che apre nuove prospettive alla funzione regolatrice delle molecole di RNA (non-coding RNAs). Infatti, anche altri RNA a funzione limitata, le particelle Vault, si è scoperto che svolgono una seconda attività, ossia vengono tagliate in frammenti che entrano in complessi ribonucleoproteici come il RISC, insieme ad enzimi Argonaute. (Persson et al, Nature Cell Biology 11, 1268 - 1271 (2009): svRNA associates with Argonaute proteins to guide sequence-specific cleavage and regulate gene expression similarly to miRNAs. It is demonstrated that svRNA downregulates CYP3A4, a key enzyme in drug metabolism.

 

A trio of researchers whose work on telomeres and telomerases has helped explain how chromosomes are copied during cell division will receive the 2009 Nobel Prize in Physiology or Medicine. Their findings have advanced medical research in cancer, inherited diseases, and aging. Elizabeth Blackburn, a biochemist at the University of California, San Francisco, Carol Greider, a geneticist at Johns Hopkins School of Medicine, and Jack Szostak, a geneticist at Harvard Medical School will share the prize equally. It is the first time two women have shared the Nobel.

 

• "I think this is a victory for curiosity-driven science," Greider, who got the call at 5AM on her way to spinning class, told The Scientist. "We are fortunate to live in a place where we can still get funding for conducting basic research to answer fundamental questions. I feel very privileged to have been able to follow my curiosity for the past 30 years."
• Scientists began to understand how genes are copied, base by base, in the 1950s, but no one could figure out why the very end of a DNA strand could not be duplicated. As a young researcher at the University of California, Berkeley, studying the chromosomes of Tetrahymena, a single cell organism that commonly lives in water, Blackburn noticed a DNA sequence, CCCCAA, that was repeated several times at the ends of the chromosomes.
• While presenting her findings at a conference in 1980, Blackburn met Szostak, who had just observed that minichromosomes, linear DNA molecules, rapidly degrade when introduced to yeast cells. The two decided to join forces - introducing the CCCCAA sequence into the minichromosomes and then injecting them into yeast cells. The sequence, named telomere, protected the minichromosomes from degradation by keeping their ends intact, indicating the existence of a previously unknown mechanism in DNA replication.
• Soon after, Blackburn and her then-graduate student, Carol Greider, found that an enzyme, telomerase, was responsible for the formation of the telomere DNA sequence. The enzyme's RNA component contained the CCCCAA sequence and served as a template for replication. Its presence allowed a DNA strand to copy itself completely from end to end.
• Blackburn, Greider, and Szostak also won the 2006 Lasker Award, often referred to as the "American Nobel." They will be presented with the Nobel Prize Medal, Diploma and $1.4 million award -- to be split three ways -- at a ceremony in Stockholm on December 10.
• The 2009 Nobel Prize in Chemistry will be awarded Wednesday, October 7.