At The University of North Carolina at Chapel Hill
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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.)