[RESEARCH HIGHLIGHTS] RNA sequencing:
FINE-TUNING PROTEIN SYNTHESIS
THE RATE OF PROTEIN PRODUCTION IN DIFFERENTIATING STEM CELLS IS CONTROLLED BY MORE COMPLEX FACTORS THAN PREVIOUSLY THOUGHT
Tweaks in the sequence of messenger RNAs (mRNAs) can influence their rate of protein production, A*STAR researchers have shown1. This process is important for how embryonic stems cells (ESCs) differentiate into other tissue types. ESCs are cells in an embryo that can develop
into any tissue in the body. Their differentiation into other cell types is controlled by protein production through regulating the expression of the genes that encode the proteins. Ribosomes are molecular machines that
translate mRNA sequences into proteins. A single gene can produce many different mRNA variants through an editing process called RNA splicing. Many of these mRNA variants produce similar but different protein variants. mRNAs contain a coding region that has an ‘untrans- lated region’ (UTR) on either end that regulates protein synthesis. “We set out to determine how changes in the
mRNA UTR sequences after splicing influence the rate at which mRNA variants are translated into proteins,” explains Leah Vardy from the A*STAR Institute of Medical Biology. By comparing the rate at which mRNA
splice variants were translated into proteins in ESCs and neural precursor cells (NPCs), a cell type into which ESCs can differentiate, Vardy’s team found that small changes in the mRNA sequence generated during splicing influence the rate of protein production of these variants. This made a big difference to their respective protein levels. “We already knew that UTRs controlled the
rate of translation, but have now shown that different splice variants within the same cell can also be translationally regulated through variations in their UTRs,” says Vardy.
8 A*STAR RESEARCH
Small splicing-regulated variations in RNA codes affect the rate of protein production in cells — a process that influences embry- onic stem cell (shown here) differentiation.
The researchers used RNA sequencing to
determine the translation rates of different variants based on the numbers of ribosomes attached to mRNAs. Those with a high load of ribosomes were considered more highly translated. The team found, for example, 31 different
genes that showed variant-specific changes in translation rates in ESCs and NPCs. They also found that, in ESCs, 10 per cent of mRNAs with multiple variants had different translation rates for each variant. The different translation rates correlated with differences in the UTR sequences, which the researchers believe are behind the variation in translation rates.
“These findings confirm an added level of
complexity where different splice variants from the same gene can be translated into proteins at very different rates within the same cell,” says Vardy. “This shows that splicing also controls the rate of protein production from specific variants, and not just protein sequence.” The team next plans to identify some
of the key regulatory sequences within UTRs to determine how they regulate the translation rate.
1. Wong, Q. W., Vaz, C., Lee, Q. Y., Zhao, T. Y., Luo, R. et al. Embryonic stem cells exhibit mRNA isoform specific translational regulation. PLoS One 11, e0143235 (2016).
ISSUE 5 | OCTOBER – DECEMBER 2016
© ROYALTYSTOCKPHOTO/SCIENCE PHOTO LIBRARY/Getty
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52