Introduction

Since our discovery of Bacillus subtilis MifM as a regulatory nascent chain that monitors the activity of the YidC-mediated membrane insertion pathway, we have been interested in and studying a class of proteins called ‘regulatory nascent chains’, which function while they are still in the midst of the process of biosynthesis. A remarkable property of this class of nascent chains is that they interact cotranslationally with components of the ribosome including those of the polypeptide exit tunnel, and thereby arrest their own translation elongation.  The arrested state of translation elongation affects translation of the target gene either positively (in the case of MifM) or negatively. Importantly, the arrest can be stabilized or canceled in response to changes in the cellular physiology that is executed by the target gene function, allowing each nascent chain to serve as a unique biological sensor to feedback-regulate the target gene expression. In the MifM regulatory system, its translation arrest is released when the nascent MifM chain, as a monitoring substrate of YidC (the regulatory target), engages in the YidC-mediated insertion into the membrane.  The regulated elongation arrest of MifM enables cells to maintain the capacity of membrane protein biogenesis.  Our interests are also focused more generally on the mechanisms of protein localization and biogenesis, the biological processes where nascent substrates undergo dynamic interactions with the machineries of translation, targeting and translocation. We believe that our research activity will contribute to the development of a new research field called “nascent chain biology”, in which we aim at understanding the still hidden principle of the central dogma of gene expression, where nascent chains are likely to play key roles.