How cells package their mRNAs

Researchers at MPIB unveiled the mechanisms with which cells protect their newly made mRNAs.

Messenger RNAs (mRNAs) are fundamental molecules of life that carry the genetic information from DNA to the protein synthesis machinery. Current biology textbooks depict mRNAs as linear chains, like elongated wool threads. Researchers at the Max Planck Institute of Biochemistry (MPIB) now illuminated a different reality. As mRNA molecules are synthesized in the nucleus, they are packaged with proteins to form compact mRNA-protein (mRNP) particles organized around a dense interaction network. Instead of resembling a thread of wool, mRNAs are wrapped up in the nucleus with a specialized set of proteins more akin balls of wool. This nuclear packaging of mRNA provides an explanation for how cells protect delicate mRNA molecules, and facilitate their transportation. The results of the current study could have far-reaching implications for medical therapies in the future, particularly in the area of mRNA-based therapeutics.

While DNA can be recovered and analyzed from Neanderthal bones that have been buried in caves for 40,000 years, mRNA molecules are inherently unstable. A single additional oxygen atom in their building blocks renders these molecules rather reactive and susceptible to ubiquitous RNases, RNA-degrading enzymes, present even on our fingertips. This instability, for example, is the reason why mRNA vaccines necessitate transportation at ultra-cold temperatures and in sterile conditions not to be damaged. But how do our cells manage to safeguard and transport their own mRNAs? The answer lies not solely within mRNA molecules themselves, but within their association with proteins as they form mRNA-protein (mRNP) particles.

Unraveling the make-up of mRNA-protein (mRNP) particles has posed a formidable biochemical hurdle, not only because of their delicate nature but also due to their remarkable diversity, complexity and dynamic properties. Despite major advances in the biochemical and structural analyses of essentially all other large RNA-protein complexes, such as ribosomes and spliceosomes, unraveling the molecular architecture of mRNPs lagged behind. In this current work, the Conti lab pushed the leading edge of mRNP biochemistry and integrative structural approaches with state-of-the-art methods, enabling molecular-level investigations of mRNPs in the model organism yeast (Saccharomyces cerevisiae). They found, that mRNPs are compact particles of proteins and RNA. Furthermore, they identified a densely connected network of proteins promoting RNA-RNA interaction within. The results of this study provide a major step forward to deciphering how cells deal with the fragility of their mRNAs, and has potentially far-reaching implications given the rapid developments of mRNA-based therapeutics.

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