In the process known as “translation,” cells build proteins based on genetic instructions. The cell has a complex set of machinery to carry out translation. Understanding how this machinery works — and what happens when its function is impaired — is a fundamental step in understanding how life works and unraveling genetic disorders that result from errors in translation.
To better understand translation, scientists in the Section on Protein Biosynthesis within the Division of Intramural Research studied blood samples from a family in which several members have a unique intellectual disability. This family’s hereditary disability results from an unusual mutation that the family members carry in a gene coding for a molecule called eIF2. eIF2 is part of a more complex molecular mechanism that scans genetic material and finds the right site to begin translating it. Because defects in eIF2 had been thought to be fatal, the researchers seized on this opportunity to study this mutation to better understand the function of eIF2 and the process of translation. To do this, they grew human and yeast cells that had the same or a similar mutation as the family’s.
The researchers found that the family’s mutation caused the eIF2 molecule to partially come apart. This partial disintegration frequently caused eIF2 to misidentify the translation starting site. The cells with this mutation also grew more slowly than normal. These findings explain how this family’s genetic mutation causes their disability and provides insight into the important role of eIF2 (PMID: 23063529).