Kojima Research Group

Capelluto Research Group (2018)

Why do you wake up everyday in the morning and go to sleep at night? What controls this behavior? How is it controlled? We are interested in deciphering genetic codes of biological rhythms to understand how the molecular clock machinery controls circadian biochemistry, physiology, and ultimately behavior.

Adaptor Proteins in Endosomal Protein Trafficking

The rotation of the earth creates a daily fluctuation of environmental cues and organisms have evolved internal timing systems, called circadian clocks, to coordinate their daily activities to anticipate and prepare for these environmental changes. The principal circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, and SCN regulates many physiological processes, such as hormone secretion, neuronal activity, physical condition, body temperature, and most obviously sleep.  Our goal is to understand how the clock machinery controls circadian biochemistry, physiology, and ultimately behavior at a molecular level. Photo Source: Allan Ajifo (CC BY 2.0).

Lipid-binding Events in the Wnt Signaling Pathway

In order to maintain daily cycles, the circadian clock must tightly regulate the rhythms of thousands of mRNAs and proteins with the correct period, phase, and amplitude to ultimately drive the wide range of rhythmic biological processes. Recent genomic approaches, however, have revealed that in many cases protein synthesis rhythms are uncoupled from mRNA rhythms, suggesting post-transcriptional regulatory mechanisms play important roles in driving circadian rhythmicity. Even after transcripts are made from DNA, subsequent processing and regulatory steps determine when, where, and how much protein will be generated, and we aim to unravel how post-transcriptional processes contribute to shape rhythmic protein expression patterns, independent of transcriptional control. Photo Source: Col Ford and Natasha de Vere (CC BY 2.0).

Modulators of Platelet Aggregation

Poly(A) tails are hallmarks of most eukaryotic mRNAs found in the 3’-end of mRNAs, and this mRNA structure is conserved from bacteria to humans. Functions of poly(A) tails are thought to protect mRNAs from degradation and promote translation initiation, although this has not been adequately addressed due to technical challenges. Using recently developed genomic technologies that have enabled us to analyze actual sequence and length of poly(A) tails, we attempt to solve the mysteries of poly(A) tails; How long do they need to be? Are functions of poly(A) tails different between organisms? Answers to these questions will also provide profound insights into how each organism evolved by adding flexibility to non-DNA-encoded structures.

Lab Members

Name
Title

Childress, Madison

Visiting Student

Gendreau, Kerry

Visitor

Gosting, Michaela

Visiting Student

Jackson, Ayana

Visiting Student

Mosig, Rebecca

Visiting Staff

Unruh, Benjamin

Visiting Student

Winkel, Brenda

Visiting Collaborator

2015

Kojima S, Green CB. Circadian genomics reveal a role for post-transcriptional regulation in mammals. Biochemistry. 2015;54(2):124–133.  http://dx.doi.org/10.1021%2Fbi500707c

Kojima S, Green CB. Analysis of circadian regulation of poly(A)-tail length. Methods Enzymol. 2015;551:387–403.  http://dx.doi.org/10.1016%2Fbs.mie.2014.10.021

2013

Godwin AR, Kojima S, Green CB, Wilusz J. Kiss your tail goodbye: the role of PARN, Nocturnin, and Angel deadenylases in mRNA biology. Biochim Biophys Acta. 2013;1829(6-7):571–579.  http://dx.doi.org/10.1016%2Fj.bbagrm.2012.12.004

2012

Kojima S, Sher-Chen EL, Green CB. Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression. Genes Dev. 2012;26(24):2724–2736.  http://dx.doi.org/10.1101%2Fgad.208306.112

2011

Douris N, Kojima S, Pan X, et al. Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes. Curr Biol. 2011;21(16):1347–1355.  http://dx.doi.org/10.1016%2Fj.cub.2011.07.018

Kojima S, Shingle DL, Green CB. Post-transcriptional control of circadian rhythms. J Cell Sci. 2011;124(Pt 3):311–320.  http://dx.doi.org/10.1242%2Fjcs.065771

Niu S, Shingle DL, Garbarino-Pico E, Kojima S, Gilbert M, Green CB. The circadian deadenylase Nocturnin is necessary for stabilization of the iNOS mRNA in mice. PLoS One. 2011;6(11):e26954.  http://dx.doi.org/10.1371%2Fjournal.pone.002695

2010

Kawai M, Green CB, Lecka-Czernik B, et al. A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation. Proc Natl Acad Sci U S A. 2010;107(23):10508–10513.  http://dx.doi.org/10.1073%2Fpnas.1000788107

Kojima S, Gatfield D, Esau CC, Green CB. MicroRNA-122 modulates the rhythmic expression profile of the circadian deadenylase Nocturnin in mouse liver. PLoS One. 2010;5(6):e11264.  http://dx.doi.org/10.1371%2Fjournal.pone.0011264

2007

Green CB, Douris N, Kojima S, et al. Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc Natl Acad Sci U S A. 2007;104(23):9888–9893.  http://dx.doi.org/10.1073%2Fpnas.0702448104

Kojima S, Matsumoto K, Hirose M, et al. LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc Natl Acad Sci U S A. 2007;104(6):1859–1864.  http://dx.doi.org/10.1073%2Fpnas.0607567104

2003

Kojima S, Hirose M, Tokunaga K, Sakaki Y, Tei H. Structural and functional analysis of 3' untranslated region of mouse Period1 mRNA. Biochem Biophys Res Commun. 2003;301(1):1–7.  http://www.ncbi.nlm.nih.gov/pubmed/12535631

2000

Kojima S, Yanagihara I, Kono G, et al. mkp-1 encoding mitogen-activated protein kinase phosphatase 1, a verotoxin 1 responsive gene, detected by differential display reverse transcription-PCR in Caco-2 cells. Infect Immun. 2000;68(5):2791–2796.  http://www.ncbi.nlm.nih.gov/pubmed/10768974