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Christopher Nicchitta

Associate Dean for Research Training and Professor
Cell Biology
(919) 684-8948
Research Interest: 
Membranes and organelles
Nucleic acid metabolism
Secretion
Research Summary: 
The spatiotemporal regulation of mRNA translation and how such regulation defines the subcellular architecture of protein synthesis.
Research Description: 

mRNA localization is a primary mechanism used by all eukaryotic cells to regulate the spatiotemporal component of gene expression - where and when an mRNA is translated to yield its encoded protein. Such regulation is critical for proper control of cell dynamics, cell signaling and cell division. Of the many mRNA localization phenomena that have been identified to date, the most prominent is mRNA localization to the endoplasmic reticulum (ER). mRNA localization to the ER is distinguished by its magnitude (ca. 30-40% of the mRNA transcriptome is localized to the ER) and temporal demands - all newly exported mRNAs undergo selection for translation in the cytosol and/or ER compartments.

In studying this question, we use a broad array of tools drawn from biochemistry, cell biology, genomics, and computational biology, and are focusing on several related themes that define this central question. Primarily, we are working to establish the rules that govern the association of mRNAs with the ER. One mechanism, in which a signal in the encoded protein leads to recruitment to the ER, has been described. The identification and characterization of additional pathways leading to ER enrichment remains a central and largely unanswered question. We are also investigating how mRNAs might directly bind to the ER independently of their association with ribosomes. In a recent paper from our lab, we have demonstrated that the mRNAs that encode the resident proteins of the endomembrane system (nuclear envelope, ER, Golgi, lysosomes, peroxisomes and plasma membrane) are localized to discrete domains of the ER and undergo direct binding interactions with components of the ER membrane components. We are keenly interested in understanding what signals and signal binding protein(s) direct this critical subset of mRNAs to this discrete subcellular location in the cell and how such localization contributes to the biogenesis of cell structure and regulation of cell function.

Publications: 
Primary role for endoplasmic reticulum-bound ribosomes in cellular translation identified by ribosome profiling.
Reid DW, Nicchitta CV.
J Biol Chem. 2012. 287:5518-27.

Hierarchical regulation of mRNA partitioning between the cytoplasm and the endoplasmic reticulum of mammalian cells.
Chen Q, Jagannathan S, Reid DW, Zheng T, Nicchitta CV.
Mol Biol Cell. 2011. 22:2646-58.

Analyzing mRNA localization to the endoplasmic reticulum via cell fractionation.
Jagannathan S, Nwosu C, Nicchitta CV.
Methods Mol Biol. 2011. 714:301-21.

Signal sequence- and translation-independent mRNA localization to the endoplasmic reticulum.
Pyhtila B, Zheng T, Lager PJ, Keene JD, Reedy MC, Nicchitta CV.
RNA. 2008. 14:445-53.

Divergent regulation of protein synthesis in the cytosol and endoplasmic reticulum compartments of mammalian cells.
Stephens SB, Nicchitta CV.
Mol Biol Cell. 2008. 19:623-32.