mRNAs are central to cellular structure and function; proper regulation of their maturation, translation, and degradation is essential for maintenance of the cellular proteome. A critical component of these processes is the regulated distribution of mRNAs between two populations: those free in the cytosol and those bound to the endoplasmic reticulum (ER). In the Nicchitta lab, we aim to understand the systems and mechanisms that regulate the partitioning of mRNAs with these two cellular compartments. Using a broad array of tools drawn from biochemistry, cell biology, genomics, and computational biology, we focus on several related problems based on this central question.

We are working to identify the mechanism(s) of mRNA localization to the endoplasmic reticulum. One mechanism, in which a signal in the encoded protein leads to mRNA recruitment to the ER, has already been described. The identification and characterization of novel pathways of mRNA localization to the ER is a primary focus of the lab. We are particularly interested in understanding the mechanisms of ribosome-independent mRNA association with the ER and why such direct organelle targeting is utilized by distinct subsets of the mRNA transcriptome. In addition, we have discovered that the regulation of mRNA translation diverges between the cytosol and ER and we are working to both describe these differences and to explain their biochemical origins. Ultimately, we aim to understand the molecular principles operating to establish the subcellular architecture of protein expression and to test the hypothesis that the partitioning of mRNAs between the cytosol and ER represents a novel mechanism for the post-transcriptional regulation of gene expression.