Human mitochondrial ribosomes can switch structural tRNAs - but when and why?

Area of Science:

• Structural biology
• Molecular genetics
• Cell biology

Background:

• Mitoribosomes are essential for protein synthesis within mitochondria.
• The structural composition of mammalian mitochondrial large ribosomal subunit (mt-LSU) was previously unknown.
• Mitochondrially encoded transfer RNAs (mt-tRNAs) are crucial for translation.

Purpose of the Study:

• To investigate the role of mt-tRNAs as structural components of mammalian mt-LSU.
• To understand the specificity and plasticity of mt-tRNA incorporation into mt-LSU.
• To explore the functional consequences of alternative mt-tRNA integration.

Main Methods:

• High-resolution cryo-electron microscopy (cryoEM) of mammalian mitoribosomes.
• Analysis of previously published data on mt-tRNA incorporation.
• Investigation of mitoribosome assembly under conditions of tRNA limitation.

Main Results:

• High-resolution cryoEM revealed mt-tRNAs as integral structural components of mammalian mt-LSU.
• Only mitochondrial tRNA^Phe and mitochondrial tRNA^Val were found to be incorporated.
• Human mitoribosomes can substitute mt-tRNA^Phe for mt-tRNA^Val when it is limiting, maintaining translational competence.

Conclusions:

• Mammalian mt-LSU exhibits plasticity in its structural mt-tRNA integration.
• This adaptability ensures the generation of translationally competent mitoribosomes.
• Further research is needed to elucidate the mechanistic and evolutionary aspects of this system.