miRNA Target for Treating Hepatitis C

Scientists from the Southwest Foundation for Biomedical Research, Santaris Pharma, and Aalborg University may have found a miRNA target for treating hepatitis C. In work appearing in Science Express this week, they show that in chimps infected with hepatitis C virus, injecting a locked nucleic acid complementary to miR-122 “leads to long-lasting suppression of HCV viremia with no evidence for viral resistance or side effects in the treated animals.” HCV needs miR-122 in order to accumulate; by turning this miRNA off, according to transcriptome analysis, they saw that genes targeted by miR-122 were turned back on and interferon-regulated genes were down-regulated.

Two studies in this week’s issue look at the structures of proteins involved in translocation and translation. In the first, scientists led by Roland Beckmann at LMU Munich and the University of Massachusetts Medical School’s Elisabet Mandon combined cryo-electron microscopy and biochemical data to find that the Sec61/SecY complex, which serves as a channel for membrane and secretory proteins during protein translation, acts alone as a monomer, and that the growing peptide occupies the complex’s central pore.

In another, Beckmann led a group that used cryo-electron microscopy to visualize the ribosome stalled during translation of the TnaC leader peptide, which is upstream of the E. coli tryptophanase operon. At 5.8 angstroms, the nascent peptide chain had a distinct conformation within the ribosome exit tunnel that led to stalling of translation. A perspective adds insight.

In more structural work, researchers led by Elizabeth Getzoff at the Scripps Institute report the structure of pyrabactin resistance 1 (PYR1), a component of the abscisic acid receptor protein that functions in early ABA signaling. The phytohormone ABA is important in seed dormancy and protecting plants against environmental stresses like drought. “Small-angle x-ray scattering suggests that ABA signals by converting PYR1 to a more compact, symmetric closed-lid dimer,” they write. A related perspective talks more about seeds and their contribution to a plant’s survival.

This week, Science announced the GE Prize Essay winner, Michael Crickmore. His essay touches on how genetic programs determine whether an animal will be big or small. “Although we know that Hox transcription factors specify the identity of individual fingers, toes, and ribs, little is known about how their individual sizes are programmed,” he writes. Crickmore did his graduate work on size at Columbia University and is now doing a postdoc with Leslie Vosshall at Rockefeller University studying how the brain works.

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