Body movement, from the muscles in your arms to the neurons transporting those signals to your brain, relies on a massive collection of proteins called molecular motors.

Fundamentally, molecular motors are proteins that convert chemical energy into mechanical movement, and have different functions depending on their task. However, because they are so small, the exact mechanisms by which these molecules coordinate with each other is poorly understood.

Publishing in Science Advances, Kyoto University’s School of Engineering has found that two types of kinesin molecular motors have different properties of coordination. Collaborating with the National Institute of Information and Communications Technology, or NICT, the findings were made possible thanks to a new tool the team developed that parks individual motors on platforms thousands of times smaller than a single cell.

“Kinesin is a motor protein that is involved in actions such as cell division, muscle contractions, and flagella movement. They move along these long protein filaments called microtubules,” explains first author Taikopaul Kaneko. “In the body, kinesins work as a team to transport large molecules inside a cell, or allow the cell itself to move.”

To observe the coordination closely, the team constructed a device consisting of an array of gold nano-pillars 50 nanometers in diameter and spaced 200 to 1000 nanometers apart. For reference, a skin cell is about 30 micrometers, or 30,000 nanometers, in diameter.

“We then combined this array with self-assembled monolayers, or SAM, that immobilized a single kinesin molecule on each nano-pillar,” continues Kaneko. “This ‘nano-patterning’ method of motor proteins gives us control of the number and spacing of kinesins, allowing us to accurately calculate how they transport microtubules.”

The team evaluated two kinesins: kinesin-1 and kinesin-14, which are involved in intercellular transport and cell division, respectively. Their results showed that in the case of kinesin-1, neither the number nor spacing of the molecules change the transport velocity of microtubules.

In contrast, kinesin-14 decreased transport velocity as the number of motors on a filament increased, but increased as the spacing of the motors increased. The results indicate that while kinesin-1 molecules work independently, kinesin-14 interacts with each other to tune the speed of transport.

Ryuji Yokokawa who led the team was surprised by the results, “Before we started this study, we thought that more motors led to faster transport and more force. But like most things in biology, it’s rarely that simple.”

The team will be using their new nano-patterning method to study the mechanics of other kinesins and different molecular motors.

“Humans have over 40 kinesins along with two other types of molecular motors called myosin and dynein. We can even modify our array to study how these motors act in a density gradient. Our results and this new tool are sure to expand our understanding of the various basic cellular processes fundamental to all life,” concludes Yokokawa.

Source: A new ‘molecular nano-patterning’ technique reveals that some molecular motors coordinate differently

Rather than directions going one-way from DNA to RNA to proteins, the latest study shows that RNA itself modulates how DNA is transcribed—using a chemical process that is increasingly apparent to be vital to biology. The discovery has significant implications for our understanding of human disease and drug design.

[…]

The picture many of us remember learning in school is an orderly progression: DNA is transcribed into RNA, which then makes proteins that carry out the actual work of living cells. But it turns out there are a lot of wrinkles.

He’s team found that the molecules called messenger RNA, previously known as simple couriers that carry instructions from DNA to proteins, were actually making their own impacts on protein production. This is done by a reversible chemical reaction called methylation; He’s key breakthrough was showing that this methylation was reversible. It wasn’t a one-time, one-way transaction; it could be erased and reversed.

“That discovery launched us into a modern era of RNA modification research, which has really exploded in the last few years,” said He. “This is how so much of gene expression is critically affected. It impacts a wide range of biological processes—learning and memory, circadian rhythms, even something so fundamental as how a cell differentiates itself into, say, a blood cell versus a neuron.”

[…]

they began to see that messenger RNA methylation could not fully explain everything they observed.

This was mirrored in other experiments. “The data coming out of the community was saying there’s something else out there, something extremely important that we’re missing—that critically impacts many early development events, as well as human diseases such as cancer,” he said.

He’s team discovered that a group of RNAs called chromosome-associated regulatory RNAs, or carRNAs, was using the same methylation process, but these RNAs do not code proteins and are not directly involved in protein translation. Instead, they controlled how DNA itself was stored and transcribed.

“This has major implications in basic biology,” He said. “It directly affects gene transcriptions, and not just a few of them. It could induce global chromatin change and affects transcription of 6,000 genes in the cell line we studied.”

He sees major implications in biology, especially in human health—everything from identifying the genetic basis of disease to better treating patients.

“There are several biotech companies actively developing small molecule inhibitors of RNA methylation, but right now, even if we successfully develop therapies, we don’t have a full mechanical picture for what’s going on,” he said. “This provides an enormous opportunity to help guide disease indication for testing inhibitors and suggest new opportunities for pharmaceuticals.”

Source: Surprise discovery shakes up our understanding of gene expression