"Junked" too soon

New roles for non-coding RNAs

Ever since 2003, when scientists completed the Human Genome Project, the prevailing view has been that less than two percent of our genetic material is dedicated to making proteins, the building blocks of cells. The rest of the genome was deemed nonfunctional, or “junk.”

Two recent HSCI studies add to the growing body of evidence that at least some of our non-protein coding genome serves a purpose, specifically during development.

In one study, co-led by geneticist John Rinn, PhD, and neurobiologist Paola Arlotta, PhD, the collaborators sought to see whether removing strands of one kind of “junk” RNA, called long intergenic noncoding RNA (lincRNA), had any effect on mouse development. The result was obvious defects in at least half of the mice born without the “junk” lincRNAs, as well as other more subtle problems.

“There has been a lot of skepticism whether these long non-coding RNAs are important for living organisms, but you can’t say this is junk without testing it,” said Rinn, based in Harvard’s Department of Stem Cell and Regenerative Biology. “We need to look at lincRNAs with the same focus we’ve applied to protein-coding genes, and see what role they play on a molecular and organismal scale.”

In a separate study, fellow Harvard scientist, Alexander Schier, PhD, examined “non-coding” RNAs in zebrafish to see whether any of them were miscategorized, and actually capable of making proteins. Schier’s lab found over 300 potential new proteins, including one, called Toddler, which promotes cell movement during zebrafish embryo development. Toddler allows cells to move faster and spread in the embryo, and zebrafish born without the protein develop with no or small hearts.

“There has been a lot of controversy over what’s coding and what’s non-coding,” Schier said. “New technologies have helped us feel confident which is which.”

Using Toddler as a proof of principle that other signaling proteins may also be hidden in “non-coding” RNAs, Schier’s lab hopes to find more proteins that explain how embryos develop.