New toolbox aids in characterizing internal ribosomal entry sites in cells

Only recent ribosomes – one of the oldest molecular machines in evolutionary terms – is recognized as an active regulator of gene expression at the level of protein biosynthesis. It is an important process for the development and function of cells, in which genetic information is converted into protein. The final stage, in which the information encountered on the Messenger RNA (MRNA) is transferred, is known as the translation.

Clinical Chemistry and Clinical Pharmacology (IKCKP) Institute at UKB. The “Immunobiochemistry” research group led by Catherine Lepech has investigated the control of translation using a direct interaction of ribosomes with MRNAS.

“As a central translation machinery which is essential for all life, the factors associated with it, such as protein or RNA structures, are focused on our research interest,” Prof., a member of the Immuniousness 2 Cluster of Excellence at Bon University. Lepak says. “The growing evidence of the fact that ribosome composition affects selective translations such as customized ribosomes preferably bind and translate some mRNAs.”

Role of Irses in gene expression

As an example of such structures, which play an important role in the initiation of translation and thus in the regulation of gene expression, Bonn researchers have now examined the internal ribosomal entry sites. These are special, folded sequences within an RNA strand that are well known well in the genetic material of the virus to kidnap the ribosomes of the host after an infection. For example, hepatitis C virus or poliovirus, all initiation for their IRES elements, are capable of starting the production of new viral proteins independently.

By recruiting ribosomes, the IRES sequence enables the initiation of translation of 5 ‘cap of MRNA independently. It is a protective cap with which its mRNA strand of the host is equipped, which enables translations under normal conditions but is blocked under viral infection.

No uniform standard for clear characteristics of IRES

The Ire was first described in the viral genome, where they allow the replica of the virus to the infected cells by recruiting host ribosomes. In recent decades, however, more and more oreses have also been described in eukaryotic cells, which are, unlike the virus, a nucleus.

“It strengthens the general approach that these elements are also included in the regulation of translation in eukaryotic cells,” says Philip Coach of Leppic Research Group in UKB and doctoral students at Bonn University. He is the first writer paper published in The Ambo Journal,

His colleague and co-writer at Bonn University, Martin Hamon, also a doctoral student also says, “However, a major challenge was the accurate and reliable characteristics of the newly described IRES, especially from eukaryotic mranas, which was difficult due to technical obstacles and artifacts associated with existing techniques.”

In its current research work, Bonn researchers have compiled and tested many versatile techniques that will simultaneously enable the strong characteristic of IRESES in the future. An important method involves the use of circular RNA reporters, which can be used to confirm the IRES-medieval activity of RNA elements.

Other techniques include determining the translation rate of MRNAS containing the quantitative staining technique of individual mRNAs in mouse fetal tissue and individual IRES.

“Such a comprehensive toolbox that can be applied to cultured cells and represents a new gold standard for strong tests and characteristics of fetal tissue orses,” coaches say. Pro. “Strong IRES elements are directly relevant to synthetic biology and emerging mRNA theraputics,” says Lepek.