A critical role for non-coding RNA GAS5 in growth arrest and rapamycin inhibition in human T-lymphocytes

2011 ◽  
Vol 39 (2) ◽  
pp. 482-486 ◽  
Author(s):  
Gwyn T. Williams ◽  
Mirna Mourtada-Maarabouni ◽  
Farzin Farzaneh
Keyword(s):  
T Lymphocytes ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Growth Arrest ◽  
Normal Growth ◽  
Functional Expression ◽  
Expression Cloning ◽  
Human T Lymphocytes ◽  
Non Coding Rna ◽  
Terminal Oligopyrimidine

Non-coding RNA GAS5 (growth arrest-specific transcript 5) is a 5′-TOP (5′-terminal oligopyrimidine tract) RNA, whose translation, and consequently also stability, is controlled by the mTOR (mammalian target of rapamycin) pathway. GAS5 was identified by functional expression cloning and is necessary and sufficient for normal growth arrest in both leukaemic and untransformed human T-lymphocytes. GAS5 is also required for the inhibitory effects of rapamycin and its analogues on T-cells. The striking functional effects of GAS5 may be mediated through the snoRNAs (small nucleolar RNAs) encoded in its introns and/or through the unusual folding of the mRNA itself, which sequesters, and therefore inhibits, the glucocorticoid receptor.

scholarly journals LARP1 is a major phosphorylation substrate of mTORC1

2018 ◽  
Author(s):  
Bruno D. Fonseca ◽  
Jian-Jun Jia ◽  
Anne K. Hollensen ◽  
Roberta Pointet ◽  
Huy-Dung Hoang ◽  
...  
Keyword(s):  
Ribosome Biogenesis ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Cellular Functions ◽  
Multiple Substrates ◽  
Eif4f Complex ◽  
Mtorc1 Pathway ◽  
Terminal Oligopyrimidine

AbstractThe mammalian target of rapamycin complex 1 (mTORC1) controls critical cellular functions such as protein synthesis, lipid metabolism, protein turnover and ribosome biogenesis through the phosphorylation of multiple substrates. In this study, we examined the phosphorylation of a recently identified target of mTORC1: La-related protein 1 (LARP1), a member of the LARP superfamily. Previously, we and others have shown that LARP1 plays an important role in repressing TOP mRNA translation downstream of mTORC1. LARP1 binds the 7-methylguanosine triphosphate (m7Gppp) cap moiety and the adjacent 5’terminal oligopyrimidine (5’TOP) motif of TOP mRNAs, thus impeding the assembly of the eIF4F complex on these transcripts. mTORC1 plays a critical role in the control of TOP mRNA translation via LARP1 but the precise mechanism by which this occurs is incompletely understood. The data described herein help to elucidate this process. Specifically, it show that: (i) mTORC1 interacts with LARP1, but not other LARP superfamily members, via the C-terminal region that comprises the DM15 domain, (ii) mTORC1 pathway controls the phosphorylation of multiple (up to 26) serine and threonine residues on LARP1 in vivo, (iii) mTORC1 regulates the binding of LARP1 to TOP mRNAs and (iv) phosphorylation of S689 by mTORC1 is particularly important for the association of the DM15 domain of LARP1 with the 5’UTR of RPS6 TOP mRNA. These data reveal LARP1 as a major substrate of mTORC1.

scholarly journals An optimized workflow for CRISPR-Cas9 deletion of surface and intracellular factors in primary human T lymphocytes

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247232
Author(s):  
Cristina Leoni ◽  
Niccolò Bianchi ◽  
Lucia Vincenzetti ◽  
Silvia Monticelli
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Gene Editing ◽  
Protein A ◽  
Surface Protein ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Lymphocytes ◽  
Human T Cell ◽  
Non Coding Rna

The appropriate regulation of T lymphocyte functions is key to achieve protective immune responses, while at the same time limiting the risks of tissue damage and chronic inflammation. Deciphering the mechanisms underpinning T cell responses in humans may therefore be beneficial for a range of infectious and chronic diseases. Recently, the development of methods based on CRISPR-Cas9 gene-editing has greatly expanded the available tool-box for the mechanistic studies of primary human T cell responses. While the deletion of a surface protein has become a relatively straightforward task, as long as an antibody for detection is available, the identification and selection of cells lacking an intracellular protein, a non-coding RNA or a protein for which no antibody is available, remain more problematic. Here, we discuss the options currently available to scientists interested in performing gene-editing in primary human T lymphocytes and we describe the optimization of a workflow for the screening and analysis of lymphocytes following gene-editing with CRISPR-Cas9 based on T cell cloning and T7 endonuclease I cleavage assay.

scholarly journals Signalling during hypoxia in human T lymphocytes - critical role of the src protein tyrosine kinase p56Lck in the O2sensitivity of Kv1.3 channels

2006 ◽  
Vol 573 (2) ◽  
pp. 357-370 ◽  
Author(s):  
Peter Szigligeti ◽  
Lisa Neumeier ◽  
Eugene Duke ◽  
Claire Chougnet ◽  
Koichi Takimoto ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Critical Role ◽  
Protein Tyrosine ◽  
Human T Lymphocytes ◽  
Kv1.3 Channels

scholarly journals Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes.

1992 ◽  
Vol 267 (12) ◽  
pp. 8650-8657 ◽  
Author(s):  
B Attali ◽  
G Romey ◽  
E Honoré ◽  
A Schmid-Alliana ◽  
M.G. Mattéi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Functional Expression ◽  
K Channels ◽  
Human T Lymphocytes

Investigations on T cell transmigration in a human skin-on-chip (SoC) model

Lab on a Chip ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 1527-1539
Author(s):  
Xiaoou Ren ◽  
Anthony E. Getschman ◽  
Samuel Hwang ◽  
Brian F. Volkman ◽  
Thomas Klonisch ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Human Skin ◽  
Drug Candidates ◽  
New Drug ◽  
Human T Lymphocytes ◽  
Quantitative Studies ◽  
Inflammatory Skin ◽  
Skin Conditions ◽  
On Chip

Our skin-on-chip (SoC) model uniquely enabled quantitative studies of transendothelial and transepithelial migration of human T lymphocytes under mimicked inflammatory skin conditions and was used to test new drug candidates.

Sign in / Sign up

Export Citation Format

Share Document