At The University of North Carolina at Chapel Hill

Research Overview

Replication dependent histone mRNAs are the only

cellular mRNA that do not end in a polyadenosine

tail.  Rather, they end in a conserved stem-loop at

their 3’ end.  These mRNAs are only present in

S-phase cells and most of the regulation is mediated

by the 3’ end of the mRNA.  Misregulation of these

mRNAs during the cell cycle has been shown to lead

to chromosomal anomalies.  These mRNAs contain

no introns and thus require only a single

endonucleolytic cleavage to form a mature message.

We utilize this system to study post-transcriptional

mRNA metabolism is various eukaryotic model

systems, including mammalian tissue culture,

Drosophila melanogaster, Xenopus and Sea Urchins.

 

Our lab has made critical discoveries about to how histone mRNAs are regulated throughout the cell cycle.  We have determined that the 3’ end of histone mRNAs is bound by Stem-Loop Binding Protein (SLBP), which is itself cell cycle regulated.  This protein plays direct roles in histone pre-mRNA 3’ end processing, export of the mature message into the cytoplasm, translation of histone mRNAs into proteins and, finally, degradation of the message as the completion of S-phase.  We have also identified novel proteins, such as SLIP1, which are required for translation of histone mRNAs and proteins, such as FLASH, which are essential for proper 3’ end processing.  Additionally, we have shown that histone mRNA degradation is triggered by  oligouridylation of the 3‘ end of the message.


Our lab is continuing to study all aspects of histone mRNA metabolism using a combination of biochemical, molecular biological and genetic approaches.  Some of our current projects include determining the full complement of factors required for proper 3‘ end formation of histone mRNAs and studying the mechanisms by which these RNAs are degraded at the end of S-phase.  Additionally, we are studying the regulation of various proteins that are necessary for the proper expression of histone mRNAs.     

Contact Us


Phone: (919) 962-2141


Marzluff Lab

207 Fordham Hall

UNC - Chapel Hill

Chapel Hill, NC 27599


marzlufflab@gmail.com (checked infrequently.  For a more prompt response, email the individual with which you want to speak.)