麻豆淫院

An international team of scientists has uncovered a surprising mechanism for how cells measure the length of messenger RNA (mRNA) tails. Rather than determining their size, cells time their growth with stopwatch-like precision. This "kinetic ruler" reveals a new principle by which cells achieve molecular accuracy in vital processes, such as gene expression.

The study is in Genes & Development.

mRNA molecules carry genetic instructions from DNA and end with a poly(A) tail, a protective string of adenosines that influences how much protein is produced and how long the message remains active. In yeast, these tails are consistently about 60 adenosines long. Until now, it was unclear how cells achieved this precision.

An international team led by the University of Turku, Finland, in collaboration with researchers from the Laboratory of Molecular Biology (LMB) in Cambridge, UK, and Aarhus University, Denmark, recreated the tail-making process in the lab.

They found that two players set the length: CPAC, the complex that adds adenosines, and Nab2, a protein that attaches to the tail and stops its growth. Once the tail is long enough, two Nab2 molecules pair up and block further extension.

Surprisingly, the final length is not set by the dimensions of the tail, but by a race between CPAC's speed of adding adenosines and Nab2's speed of binding.

"These molecular machines measure RNA not by size, but by timing. The precision comes from stopping the reaction always between two and three seconds after it begins," explains lead author Dr. Matti Turtola from the University of Turku.

In this stopwatch-like system, the concentration of Nab2 in the cell鈥攁nd therefore its binding speed鈥攄etermines when tail extension stops.

"It's an elegant mechanism. What's remarkable is that Nab2 also regulates its own levels, keeping the timing precisely calibrated even when conditions change," Turtola adds.

This timing-based "kinetic ruler" is critical because the starting length of the poly(A) tail determines how much protein an mRNA can produce and how long the message lasts. By ensuring every new mRNA gets the right-sized tail, cells keep protein production under control.

The discovery highlights the precision with which cells control gene expression, showing that timing-based mechanisms can be just as important as structural ones in molecular biology.

Similar kinetic rulers may operate in many other biological processes, and understanding them could help explain how disruptions in timing lead to disease.

In humans, the Nab2 counterpart ZC3H14 is required for brain development, hinting that these timing-based mechanisms may also be essential for maintaining balanced gene expression in human cells.