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The RNA insurrection: Genes' "humble servant" rules from behind the scenes

A once-unimagined class of molecules is playing a bigger part than anybody thought in the running of intracellular life. Most surprising is that these molecules are not proteins, the proletarian workhorses of every cell. They are instead made of RNA, traditionally dismissed as a mere messenger from a cell's nucleus to its outermost regions. RNA's day job, it was long agreed, was to convey verbatim recipes - no ad-libbing! - from DNA in the nuclear throne room to molecular chefs situated in the provinces who, upon reading those instructions, served up proteins to order.

Biochemist Tom Cech, PhD, who started teaching at the University of Colorado in Boulder right around the time I started learning there, blew a big hole in what was then called The Central Dogma of Molecular Biology: DNA makes RNA makes protein. Cech won the Nobel Prize in 1989 (and sent a generation of textbooks to meet their shredder) for showing that RNA itself can perform as a chemical catalyst.

But that RNA finding was just the start of something big. The University of Massachusetts' Craig Mello, PhD, cut his grad-student teeth at the U. of Colorado under the same professors I had as an undergraduate. Mello and Stanford's Andy Fire, PhD, shared a Nobel in 2006 for discovering a class of small RNA molecules that can fine-tune the production of proteins at the sites where they're being manufactured.

And now we learn (see my Stanford Medicine article on the subject) of a class of molecules made of RNA that shows that this substance, even when it doesn't code for proteins, is as protean as you can get. So-called "lincRNA" (for long, intergenic noncoding RNA) has the capacity to determine which genes inside a cell get expressed (i.e., which ones are copied into "messenger RNA") and which remain silent. That's the key to what makes a skin cell a skin cell, or distinguishes an active immune cell from a resting one - even though they all have the same DNA and, thus, the same genes.

The latest discovery along these lines, just published in Nature Genetics, indicates that lincRNA is a critical regulator of somatic cell reprogramming - the conversion of one type of cell (say, a skin cell) to another type (for instance, an embryonic-stem-cell like cell that goes by the name of "induced pluripotent stem cells" or iPS cells). That's about the hottest field in science today.

In fact, according to a new Nature article, researchers have even succeeded in converting human fibroblasts (easily obtained from skin) into blood progenitor cells (which ordinarily have to be extracted from bone marrow). No need to reprogram those cells all the way back to their primitive iPS status and then fast-forward them down another differentiation pathway. This is the essence of the regenerative medicine of the future.

A word of thanks to Dick McIntosh, PhD; Mike Yarus, PhD; Larry Gold, PhD; Larry Soll, PhD; and my other phenomenal U. of Colorado biology teachers back around the turn of the '80s. And not just for what they taught me personally.

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