mRNA translation biology
The Selectivity of Translation Biology
The biology of mRNA translation is an emerging science of the last decade. At Anima Biotech, we are experts in this science.
Our target space encompasses proteins that have specific biological roles in coordinating and regulating translation of individual mRNAs and pathways, allowing for the discovery of small molecules that selectively modulate the translation of almost any protein of interest.
Anima's translation modulators can be tissue or disease-specific
Our small molecules are targeting novel proteins involved in the regulation of mRNA translation
Protein synthesis is a high energy consuming process. The translation machinery, therefore, must pose the ability to respond rapidly to various environmental cues, to conserve energy. Subsequently, distinct mechanisms enabling cells to respond quickly and efficiently to extracellular signals have evolved. These mechanisms include:
- Coordinated changes in translation initiation such as changing the components of the initiation complex
- Shuttling of mRNA, in a protected manner, to different cellular compartments where their translation is needed
- The use of non-protein vehicles to regulate mRNA stability, such as short lived small noncoding RNAs (termed microRNA)
In different tissues, cells need to respond to distinct sets of cues. For example, mRNA translation in neurons is localized to different cellular compartments. Ribosomes are located around the nucleus, along exons and at nerve endings to enable supply on demand of specific proteins required at these different cellular locations. Thus, to enable these diverse requirements and responses, mRNA translation has developed elaborate, tissue specific and mRNA selective regulatory systems.
Biology
mRNA translation is a highly regulated process: once mRNA is transcribed, it is bound by RNA binding proteins (RBPs) in a highly specific and selective manner. An additional layer of regulation is mediated by modifications of ribonucleotides in mRNA (epitranscriptomics), that modulate RBP-mRNA interactions. Together, these mechanisms regulate mRNA processing, nuclear export and mRNA steady state levels. RBPs regulate the localization of mRNAs in the nucleus and cytoplasm, thereby determining mRNA translation in a temporal and spatial manner. Moreover, ribosomes, much like RNA polymerases and proteasomes, have accessory proteins associated with them in a tissue and signal-specific manner. This lends mRNA translation an additional layer of selectivity.
Bi-directional mRNA translation regulation
Targeting the regulatory mechanisms of mRNA translation enables the discovery of compounds that not only decrease but can also increase protein translation in a selective manner.
The images below are taken from Anima’s Collagen I program. During the screening campaign, both COL1A1 mRNA translation inhibitors and activators were identified.
A compound which reduces the rate of translation of Collagen I, decreases the light. Subsequently, this compound reduces Collagen I protein accumulation (middle panel).
A compound which enhances the rate of translation of Collagen I, increases the light. The compound also enhances production of Collagen I protein (right panel).