Putting the spotlight on translation initiation

Most of the cell’s energy is expended for protein synthesis. Despite this,
it has been a major challenge to monitor protein synthesis on individual
RNAs across the whole transcriptome. This changed with the introduction of
ribosome profiling, a method that captured all translating ribosomes and
mapped them back to their exact position in the transcriptome. Since its
inception this technique has become a standard for studying translational
regulation. Despite its usefulness, ribosome profiling has a major
limitation: it is completely blind to what happens during the initiation
phase of translation. Initiation is a rate limiting step in protein
synthesis and it is here, during this phase, that much of the process is
regulated. This drawback therefore results in a blindspot for researchers
trying to understand how protein synthesis is controlled.

A new study from the Valen Lab puts the spotlight onto translation
initiation. Published in Cell Reports this work introduces a new method
called Ribosome Complex Profiling (RCP-seq) to study scanning ribosomes as
they initiate translation. Spanning both computational and experimental
work the study is the product of two Valen lab members: Adam Giess and
Yamila Torres Cleuren. The study sheds light on how ribosomes are recruited
to RNAs, and quantifies how effectively they traverse and scan through the
5’ UTRs. Like ribosome profiling, RCP-seq also captures all translating
ribosomes and can therefore measure how scanning ribosomes recognize the
start codon and progress to the elongation phase. This new perspective
revealed how cells can modulate initiation by changing the context around
the start codon. Together, RCP-seq presents a new window into translation
initiation and is poised to reveal many of the secrets of how initiation is
regulated.

Available at: https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30434-4