Kenan Distinguished Professor of Biochemistry and Biophysics
Biology – joint appointment
(PhD – Duke University)
Accepting rotation students: joint project with Dr. Bob Duronio. Topic will be: Biochemical and genetic analysis of histone mRNA processing and histone locus body formation in Drosophila.
HONORS & AWARDS
- UNC School of Medicine Executive Associate Dean for Research, 1997-2010
- Kenan Distinguished Professorship, 2002
Regulation of Gene Activity
My research interests are focused on the regulation of gene activity in animal cells, in particular regulation of gene expression during the cell cycle by postranscriptional mechanisms. One system we study is the regulation of histone mRNA, both during the mammalian cell cycle and during early development in frogs and sea urchins. Histone mRNAs are the only mRNAs which do not have poly(A)+ tails, ending instead in a conserved stem-loop structure. Histone mRNAs are present only in S-phase cells and most of the regulation is mediated by the 3′ end of histone mRNA. Histone genes lack introns, and histone mRNA is formed by a single processing reaction, cleavage form the 3′ end of the histone mRNA. The mRNA is then immediately transported to the cytoplasm. Both the cleavage reaction to form histone mRNA and the half-life of the histone mRNA are regulated during the cell cycle. We have cloned the cDNA for the stem-loop binding protein (SLBP) that binds the 3′ end of histone mRNA and participates in all aspects of histone mRNA metabolism. SLBP is a critical factor involved in regulating histone mRNA levels. Our current interests are in understanding how SLBP carries out its multiple functions; RNA binding, 3′ processing, transport, stimulator of translation and regulating histone mRNA half-life. In addition, we are studying how SLBP itself is regulated and how this regulation connects the other cell cycle regulators with the regulation of histone mRNA.
In embryos, which undergo a very rapid series of cell divisions after fertilization, there is an exponentially increasing demand for histones to assemble the newly replicated DNA into chromatin. During this time the histone mRNAs are not cell-cycle regulated but are stable for multiple cell cycles. We have cloned embryo specific SLBPs from these stages and are determining how they function to regulate histone mRNA metabolism in frog and sea urchin embryos. We are also studying the role of the G1 cyclins, cyclin D and cyclin E in the regulation of these early cell cycles which lack gap phases.
SELECTED PUBLICATIONS (click for Full Publication List)
A standardized nomenclature for mammalian histone genes. Seal RL, Denny P, Bruford EA, Gribkova AK, Landsman D, Marzluff WF, McAndrews M, Panchenko AR, Shaytan AK, Talbert PB.
Epigenetics Chromatin. 2022 Oct 1;15(1):34. doi: 10.1186/s13072-022-00467-2. PMID: 36180920 Free PMC article. Review.
Knockouts of TUT7 and 3’hExo show that they cooperate in histone mRNA maintenance and degradation. Holmquist CE, He W, Meganck RM, Marzluff WF. RNA. 2022 Nov;28(11):1519-1533. doi: 10.1261/rna.079233.122. Epub 2022 Aug 30. PMID: 36041871 Free PMC article.
Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection. Tse LV, Meganck RM, Araba KC, Yount BL, Shaffer KM, Hou YJ, Munt JE, Adams LE, Wykoff JA, Morowitz JM, Dong S, Magness ST, Marzluff WF, Gonzalez LM, Ehre C, Baric RS. Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2118126119. doi: 10.1073/pnas.2118126119. Epub 2022 Apr 27. PMID: 35476513 Free PMC article.
Reconstitution and biochemical assays of an active human histone pre-mRNA 3′-end processing machinery. Sun Y, Aik WS, Yang XC, Marzluff WF, Dominski Z, Tong L. Methods Enzymol. 2021;655:291-324. doi: 10.1016/bs.mie.2021.03.021. Epub 2021 May 3. PMID: 34183127 Free PMC article.
Superresolution light microscopy of the Drosophila histone locus body reveals a core-shell organization associated with expression of replication-dependent histone genes.
Kemp JP Jr, Yang XC, Dominski Z, Marzluff WF, Duronio RJ. Mol Biol Cell. 2021 Apr 19;32(9):942-955. doi: 10.1091/mbc.E20-10-0645. Epub 2021 Mar 31. PMID: 33788585 Free PMC article.
Engineering highly efficient backsplicing and translation of synthetic circRNAs. Meganck RM, Liu J, Hale AE, Simon KE, Fanous MM, Vincent HA, Wilusz JE, Moorman NJ, Marzluff WF, Asokan A. Mol Ther Nucleic Acids. 2021 Jan 16;23:821-834. doi: 10.1016/j.omtn.2021.01.003. eCollection 2021 Mar 5. PMID: 33614232 Free PMC article.
Dual RNA 3′-end processing of H2A.X messenger RNA maintains DNA damage repair throughout the cell cycle. Griesbach E, Schlackow M, Marzluff WF, Proudfoot NJ. Nat Commun. 2021 Jan 13;12(1):359. doi: 10.1038/s41467-020-20520-6. PMID: 33441544 Free PMC article.
A region of SLBP outside the mRNA-processing domain is essential for deposition of histone mRNA into the Drosophila egg. Potter-Birriel JM, Gonsalvez GB, Marzluff WF. J Cell Sci. 2021 Feb 11;134(3):jcs251728. doi: 10.1242/jcs.251728. PMID: 33408246 Free PMC article.
CRL4DCAF1/VprBP E3 ubiquitin ligase controls ribosome biogenesis, cell proliferation, and development. Han XR, Sasaki N, Jackson SC, Wang P, Li Z, Smith MD, Xie L, Chen X, Zhang Y, Marzluff WF, Xiong Y. Sci Adv. 2020 Dec 18;6(51):eabd6078. doi: 10.1126/sciadv.abd6078. Print 2020 Dec. PMID: 33355139 Free article.
CDK-Regulated Phase Separation Seeded by Histone Genes Ensures Precise Growth and Function of Histone Locus Bodies.
Hur W, Kemp JP Jr, Tarzia M, Deneke VE, Marzluff WF, Duronio RJ, Di Talia S. Dev Cell. 2020 Aug 10;54(3):379-394.e6. doi: 10.1016/j.devcel.2020.06.003. Epub 2020 Jun 23. PMID: 32579968 Free PMC article.