Life Sciences Research for Lifelong Health

Martin Turner

Research Summary

The molecular processes which control the development and function of lymphocytes have been extensively studied from the perspective of cell surface receptors and their associated intracellular signalling.

Also, many transcription factors which repress or promote the production of mRNA have been identified as being essential for lymphocyte development and activation.  These studies have revealed that genes, molecules and pathways that are used early in the development of lymphocytes are re-used in fully mature cells as part of the response to infection.

We are developing tools for measuring gene expression in rare cell populations.  We also use genome wide approaches to study RNA turnover and translation and to identify the targets of RNA binding proteins.

We aim to characterise fundamental mechanisms controlling lymphocyte development and function throughout the life-course.  These include understanding the roles of RNA binding proteins in lymphocyte development and activation. 

In the future explaining how these are integrated with signal transduction pathways, microRNA and transcription factor networks will be an important step towards a systems level understanding of immunity.

 


Latest Publications

RNA-binding proteins mind the GAPs.
Turner M, Monzón-Casanova E

Nature immunology, 18, 1529-2916, 146-148, 2017

PMID: 28102216

The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic β-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression.
Vogel KU, Bell LS, Galloway A, Ahlfors H, Turner M

The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly to enforce the β-selection checkpoint during thymopoiesis, yet their molecular targets remain largely unknown. In this study, we identify these targets on a genome-wide scale in primary mouse thymocytes and show that Zfp36l1/l2 regulate DNA damage response and cell cycle transcripts to ensure proper β-selection. Double-negative 3 thymocytes lacking Zfp36l1/l2 share a gene expression profile with postselected double-negative 3b cells despite the absence of intracellular TCRβ and reduced IL-7 signaling. Our findings show that in addition to controlling the timing of proliferation at β-selection, posttranscriptional control by Zfp36l1/l2 limits DNA damage responses, which are known to promote thymocyte differentiation. Zfp36l1/l2 therefore act as posttranscriptional safeguards against chromosomal instability and replication stress by integrating pre-TCR and IL-7 signaling with DNA damage and cell cycle control.

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Journal of immunology (Baltimore, Md. : 1950), , 1550-6606, , 2016

PMID: 27566829

The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation.
Tiedje C, Diaz-Muñoz MD, Trulley P, Ahlfors H, Laaß K, Blackshear PJ, Turner M, Gaestel M

RNA-binding proteins (RBPs) facilitate post-transcriptional control of eukaryotic gene expression at multiple levels. The RBP tristetraprolin (TTP/Zfp36) is a signal-induced phosphorylated anti-inflammatory protein guiding unstable mRNAs of pro-inflammatory proteins for degradation and preventing translation. Using iCLIP, we have identified numerous mRNA targets bound by wild-type TTP and by a non-MK2-phosphorylatable TTP mutant (TTP-AA) in 1 h LPS-stimulated macrophages and correlated their interaction with TTP to changes at the level of mRNA abundance and translation in a transcriptome-wide manner. The close similarity of the transcriptomes of TTP-deficient and TTP-expressing macrophages upon short LPS stimulation suggested an effective inactivation of TTP by MK2, whereas retained RNA-binding capacity of TTP-AA to 3'UTRs caused profound changes in the transcriptome and translatome, altered NF-κB-activation and induced cell death. Increased TTP binding to the 3'UTR of feedback inhibitor mRNAs, such as Ier3, Dusp1 or Tnfaip3, in the absence of MK2-dependent TTP neutralization resulted in a strong reduction of their protein synthesis contributing to the deregulation of the NF-κB-signaling pathway. Taken together, our study uncovers a role of TTP as a suppressor of feedback inhibitors of inflammation and highlights the importance of fine-tuned TTP activity-regulation by MK2 in order to control the pro-inflammatory response.

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Nucleic acids research, , 1362-4962, , 2016

PMID: 27220464

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Latest Publications

RNA-binding proteins mind the GAPs.

Turner M, Monzón-Casanova E

Nature immunology
18 1529-2916:146-148 (2017)

PMID: 28102216

The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation.

Tiedje C, Diaz-Muñoz MD, Trulley P

Nucleic acids research
1362-4962: (2016)

PMID: 27220464

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

Galloway A, Saveliev A, Łukasiak S

Science (New York, N.Y.)
352 1095-9203:453-9 (2016)

PMID: 27102483

MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis.

Nakagawa R, Leyland R, Meyer-Hermann M

The Journal of clinical investigation
1558-8238: (2015)

PMID: 26657861

GIMAP1 Is Essential for the Survival of Naive and Activated B Cells In Vivo.

Webb LM, Datta P, Bell SE

Journal of immunology (Baltimore, Md. : 1950)
1550-6606: (2015)

PMID: 26621859

Generation of functionally distinct isoforms of PTBP3 by alternative splicing and translation initiation.

Tan LY, Whitfield P, Llorian M

Nucleic acids research
1362-4962: (2015)

PMID: 25940628

The RNA-binding protein HuR is essential for the B cell antibody response.

Diaz-Muñoz MD, Bell SE, Fairfax K

Nature immunology
16 1529-2916:415-25 (2015)

PMID: 25706746

Deletion of AU-Rich Elements within the Bcl2 3'UTR Reduces Protein Expression and B Cell Survival In Vivo.

Díaz-Muñoz MD, Bell SE, Turner M

PloS one
10 1932-6203:e0116899 (2015)

PMID: 25680182

PI3K Signaling in B Cell and T Cell Biology.

Okkenhaug K, Turner M, Gold MR

Frontiers in immunology
5 1664-3224:557 (2014)

PMID: 25404931

Generation and characterisation of mice deficient in the multi-GTPase domain containing protein, GIMAP8.

Webb LM, Pascall JC, Hepburn L

PloS one
9 1932-6203:e110294 (2014)

PMID: 25329815

The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.

Lu D, Nakagawa R, Lazzaro S

The Journal of experimental medicine
211 1540-9538:2183-98 (2014)

PMID: 25288398