Mechanisms and control of protein translation in the kidney.

Translational control of protein synthesis is critical for cell division, homeostasis and survival. Recent data indicate that dysregulation of protein synthesis that leads to either increased or decreased expression of specific proteins contributes to the manifestations of various kidney diseases. Most of the control of protein synthesis occurs in the first or initiation phase, which is also the most complicated. Following the initiation phase is the elongation phase where the peptide chain is formed. RNA transcripts are released from ribosomes after the termination phase. Transcripts can be translated in a cap-dependent or cap-independent manner. The mTOR (mammalian target of rapamycin) cascade regulates translation of most cap-dependent transcripts at the level of initiation and elongation, which represents 95% of total transcripts. During specific events (e.g. mitosis, stress cell survival) control of the less-common cap-independent transcripts occurs which allows the cell to adapt to the new state. Activation of stress kinases and inactivation of the mTOR pathway are at the center of this adaptive mechanism. Recent studies have elucidated the role of micro-RNAs (miRs) in controlling translation. miRs bind directly to specific transcripts and most often directly reduce translation; however, by targeting other positive or negative regulators of the pathways regulating protein synthesis they may indirectly affect synthetic levels of other transcripts. Several examples are described below in which these mechanisms are intertwined and act together to dysregulate protein synthesis in the diseased kidney.