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Article ; Online: Noncoding RNA: linking microRNAs to their targets.

Grimson, Andrew

2015 Volume 11, Issue 2, Page(s) 100–101

MeSH term(s)	Cell Differentiation/genetics ; Humans ; MicroRNAs ; RNA, Long Noncoding ; Transcriptome
Chemical Substances	H19 long non-coding RNA ; MIRN106 microRNA, human ; MicroRNAs ; RNA, Long Noncoding
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/nchembio.1741
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Article ; Online: Small RNAs and their protein partners in animal meiosis.

Carro, María de Las Mercedes / Grimson, Andrew / Cohen, Paula E

Current topics in developmental biology

2022 Volume 151, Page(s) 245–279

Abstract: Meiosis is characterized by highly regulated transitions in gene expression that require diverse mechanisms of gene regulation. For example, in male mammals, transcription undergoes a global shut-down in early prophase I of meiosis, followed by ... ...

Abstract	Meiosis is characterized by highly regulated transitions in gene expression that require diverse mechanisms of gene regulation. For example, in male mammals, transcription undergoes a global shut-down in early prophase I of meiosis, followed by increasing transcriptional activity into pachynema. Later, as spermiogenesis proceeds, the histones bound to DNA are replaced with transition proteins, which are themselves replaced with protamines, resulting in a highly condensed nucleus with repressed transcriptional activity. In addition, two specialized gene silencing events take place during prophase I: meiotic silencing of unsynapsed chromatin (MSUC), and the sex chromatin specific mechanism, meiotic sex chromosome inactivation (MSCI). Notably, conserved roles for the RNA binding protein (RBP) machinery that functions with small non-coding RNAs have been described as participating in these meiosis-specific mechanisms, suggesting that RNA-mediated gene regulation is critical for fertility in many species. Here, we review roles of small RNAs and their associated RBPs in meiosis-related processes such as centromere function, silencing of unpaired chromatin and meiotic recombination. We will discuss the emerging evidence of non-canonical functions of these components in meiosis.
MeSH term(s)	Animals ; Male ; Sex Chromosomes/genetics ; Chromatin/genetics ; Meiosis/genetics ; Histones/genetics ; RNA ; Mammals/genetics ; Mammals/metabolism
Chemical Substances	Chromatin ; Histones ; RNA (63231-63-0)
Language	English
Publishing date	2022-07-25
Publishing country	United States
Document type	Review ; Journal Article
ISSN	1557-8933 ; 0070-2153
ISSN (online)	1557-8933
ISSN	0070-2153
DOI	10.1016/bs.ctdb.2022.06.001
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Article ; Online: Dynamic and widespread control of poly(A) tail length during macrophage activation.

Kwak, Yeonui / Daly, Ciarán W P / Fogarty, Elizabeth A / Grimson, Andrew / Kwak, Hojoong

RNA (New York, N.Y.)

2022 Volume 28, Issue 7, Page(s) 947–971

Abstract: The poly(A) tail enhances translation and transcript stability, and tail length is under dynamic control during cell state transitions. Tail regulation plays essential roles in translational timing and fertilization in early development, but poly(A) tail ...

Abstract	The poly(A) tail enhances translation and transcript stability, and tail length is under dynamic control during cell state transitions. Tail regulation plays essential roles in translational timing and fertilization in early development, but poly(A) tail dynamics have not been fully explored in post-embryonic systems. Here, we examined the landscape and impact of tail length control during macrophage activation. Upon activation, more than 1500 mRNAs, including proinflammatory genes, underwent distinctive changes in tail lengths. Increases in tail length correlated with mRNA levels regardless of transcriptional activity, and many mRNAs that underwent tail extension encode proteins necessary for immune function and post-transcriptional regulation. Strikingly, we found that
MeSH term(s)	Gene Expression Regulation ; Macrophage Activation/genetics ; Poly A/genetics ; Poly A/metabolism ; Polyadenylation ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	RNA, Messenger ; Poly A (24937-83-5)
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1241540-6
ISSN	1469-9001 ; 1355-8382
ISSN (online)	1469-9001
ISSN	1355-8382
DOI	10.1261/rna.078918.121
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Article ; Online: A targeted approach to miRNA target identification.

Grimson, Andrew

Nature methods

2010 Volume 7, Issue 10, Page(s) 795–797

MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Mass Spectrometry/methods ; MicroRNAs/genetics ; Proteomics/methods
Chemical Substances	Caenorhabditis elegans Proteins ; MicroRNAs
Language	English
Publishing date	2010-09-29
Publishing country	United States
Document type	Comment ; News
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/nmeth1010-795
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Article ; Online: Characterizing mRNA Sequence Motifs in the 3'-UTR Using GFP Reporter Constructs.

Geissler, Rene / Grimson, Andrew

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1720, Page(s) 77–88

Abstract: GFP reporter constructs are widely used as an expression system for studying the function of regulatory sequence motifs (cis elements) within the 3'-UTRs (3' untranslated regions) of mRNAs. Here we provide details on the characterization of individual ... ...

Abstract	GFP reporter constructs are widely used as an expression system for studying the function of regulatory sequence motifs (cis elements) within the 3'-UTRs (3' untranslated regions) of mRNAs. Here we provide details on the characterization of individual sequence motifs, which typically regulate mRNA decay and translation. In addition, we describe methods to identify trans factors required for the function of such elements. To facilitate efficient identification of novel functional 3'-UTR motifs, we describe a screening approach based on dual-color fluorescence reporter constructs. Such screening approaches can be used to test large collections of defined sequence or libraries of random sequences.
MeSH term(s)	3' Untranslated Regions/genetics ; Base Sequence/genetics ; Cell Line ; Fluorescence ; Genes, Reporter ; Genomics/methods ; Green Fluorescent Proteins/chemistry ; Humans ; Protein Biosynthesis/genetics ; RNA Processing, Post-Transcriptional ; RNA Stability/genetics ; RNA, Messenger/chemistry ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Sequence Analysis, RNA/methods
Chemical Substances	3' Untranslated Regions ; RNA, Messenger ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2017-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7540-2_6
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Article ; Online: A TOPBP1 allele causing male infertility uncouples XY silencing dynamics from sex body formation.

Ascenção, Carolline / Sims, Jennie R / Dziubek, Alexis / Comstock, William / Fogarty, Elizabeth A / Badar, Jumana / Freire, Raimundo / Grimson, Andrew / Weiss, Robert S / Cohen, Paula E / Smolka, Marcus B

eLife

2024 Volume 12

Abstract: Meiotic sex chromosome inactivation (MSCI) is a critical feature of meiotic prophase I progression in males. While the ATR kinase and its activator TOPBP1 are key drivers of MSCI within the specialized sex body (SB) domain of the nucleus, how they ... ...

Abstract	Meiotic sex chromosome inactivation (MSCI) is a critical feature of meiotic prophase I progression in males. While the ATR kinase and its activator TOPBP1 are key drivers of MSCI within the specialized sex body (SB) domain of the nucleus, how they promote silencing remains unclear given their multifaceted meiotic functions that also include DNA repair, chromosome synapsis, and SB formation. Here we report a novel mutant mouse harboring mutations in the TOPBP1-BRCT5 domain.
MeSH term(s)	Animals ; Humans ; Male ; Mice ; Alleles ; Carrier Proteins/genetics ; DNA Repair ; DNA-Binding Proteins/genetics ; Infertility, Male/genetics ; Meiosis ; Nuclear Proteins/genetics ; Sex Chromosomes
Chemical Substances	Carrier Proteins ; DNA-Binding Proteins ; Nuclear Proteins ; TOPBP1 protein, human ; Topbp1 protein, mouse
Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.90887
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Article ; Online: Functionalized nanowires for miRNA-mediated therapeutic programming of naïve T cells.

Yee Mon, Kristel J / Kim, Sungwoong / Dai, Zhonghao / West, Jessica D / Zhu, Hongya / Jain, Ritika / Grimson, Andrew / Rudd, Brian D / Singh, Ankur

Nature nanotechnology

2024

Abstract: Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic- ... ...

Abstract	Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8
Language	English
Publishing date	2024-04-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2254964-X
ISSN	1748-3395 ; 1748-3387
ISSN (online)	1748-3395
ISSN	1748-3387
DOI	10.1038/s41565-024-01649-7
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Article ; Online: Neonatal CD8+ T Cells Resist Exhaustion during Chronic Infection.

Maymí, Viviana I / Zhu, Hongya / Jager, Mason / Johnson, Shawn / Getchell, Rodman / Casey, James W / Grenier, Jennifer K / Wherry, E John / Smith, Norah L / Grimson, Andrew / Rudd, Brian D

Journal of immunology (Baltimore, Md. : 1950)

2024 Volume 212, Issue 5, Page(s) 834–843

Abstract: Chronic viral infections, such as HIV and hepatitis C virus, represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections, the underlying mechanisms remain unknown. In ... ...

Abstract	Chronic viral infections, such as HIV and hepatitis C virus, represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections, the underlying mechanisms remain unknown. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (lymphocytic choriomeningitis virus clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially became effector cells early in chronic infection compared with adult CD8+ T cells and expressed higher levels of genes associated with cell migration and effector cell differentiation. During the chronic phase of infection, the neonatal cells retained more immune functionality and expressed lower levels of surface markers and genes related to exhaustion. Because the neonatal cells protect from viral replication early in chronic infection, the altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influence key cell fate decisions during chronic infection.
MeSH term(s)	Mice ; Animals ; Lymphocytic Choriomeningitis ; Persistent Infection ; Lymphocytic choriomeningitis virus ; CD8-Positive T-Lymphocytes ; Cell Differentiation ; Mice, Inbred C57BL ; Chronic Disease
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300396
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Article ; Online: Evolutionary dynamics of microRNA target sites across vertebrate evolution.

Simkin, Alfred / Geissler, Rene / McIntyre, Alexa B R / Grimson, Andrew

PLoS genetics

2020 Volume 16, Issue 2, Page(s) e1008285

Abstract: MicroRNAs (miRNAs) control the abundance of the majority of the vertebrate transcriptome. The recognition sequences, or target sites, for bilaterian miRNAs are found predominantly in the 3' untranslated regions (3'UTRs) of mRNAs, and are amongst the most ...

Abstract	MicroRNAs (miRNAs) control the abundance of the majority of the vertebrate transcriptome. The recognition sequences, or target sites, for bilaterian miRNAs are found predominantly in the 3' untranslated regions (3'UTRs) of mRNAs, and are amongst the most highly conserved motifs within 3'UTRs. However, little is known regarding the evolutionary pressures that lead to loss and gain of such target sites. Here, we quantify the selective pressures that act upon miRNA target sites. Notably, selective pressure extends beyond deeply conserved binding sites to those that have undergone recent substitutions. Our approach reveals that even amongst ancient animal miRNAs, which exert the strongest selective pressures on 3'UTR sequences, there are striking differences in patterns of target site evolution between miRNAs. Considering only ancient animal miRNAs, we find three distinct miRNA groups, each exhibiting characteristic rates of target site gain and loss during mammalian evolution. The first group both loses and gains sites rarely. The second group shows selection only against site loss, with site gains occurring at a neutral rate, whereas the third loses and gains sites at neutral or above expected rates. Furthermore, mutations that alter the strength of existing target sites are disfavored. Applying our approach to individual transcripts reveals variation in the distribution of selective pressure across the transcriptome and between miRNAs, ranging from strong selection acting on a small subset of targets of some miRNAs, to weak selection on many targets for other miRNAs. miR-20 and miR-30, and many other miRNAs, exhibit broad, deeply conserved targeting, while several other comparably ancient miRNAs show a lack of selective constraint, and a small number, including mir-146, exhibit evidence of rapidly evolving target sites. Our approach adds valuable perspective on the evolution of miRNAs and their targets, and can also be applied to characterize other 3'UTR regulatory motifs.
MeSH term(s)	3' Untranslated Regions/genetics ; Animals ; Binding Sites/genetics ; Evolution, Molecular ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; MicroRNAs/metabolism ; Mutation ; RNA, Messenger/genetics ; Selection, Genetic ; Transcriptome/genetics
Chemical Substances	3' Untranslated Regions ; MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2020-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1008285
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Article ; Online: A position-specific 3'UTR sequence that accelerates mRNA decay.

Geissler, Rene / Grimson, Andrew

RNA biology

2016 Volume 13, Issue 11, Page(s) 1075–1077

Abstract: The 3' untranslated regions (3'UTRs) of mammalian mRNAs direct an extensive range of alternative post-transcriptional outcomes, including regulation of mRNA decay and translation, contributing significantly to overall gene regulation. However, our ... ...

Abstract	The 3' untranslated regions (3'UTRs) of mammalian mRNAs direct an extensive range of alternative post-transcriptional outcomes, including regulation of mRNA decay and translation, contributing significantly to overall gene regulation. However, our knowledge of the underlying sequences and mechanisms is incomplete. We identified a novel 3'UTR sequence motif in mammals that targets mRNAs for transcript degradation. The motif is found in hundreds of mRNAs and is enriched in transcripts encoding regulatory proteins, such as transcription and signaling factors. Degradation of mRNAs containing the motif is mediated by the CCR4-NOT deadenylation complex. We identified hnRNPs A1 and A2/B1 as trans factors that directly bind to the motif, indicating a novel role for these proteins in deadenylation. Interestingly, a genome-wide analysis of the impact of this new regulatory pathway showed that the most active motifs are located within the 5' and 3'-terminal portions of 3'UTRs, whereas elements in the center tend to be inactive. The highly position-specific function of the motif adds a new layer of regulation to gene expression mediated by 3'UTRs.
MeSH term(s)	3' Untranslated Regions ; Animals ; Gene Expression Regulation ; Heterogeneous Nuclear Ribonucleoprotein A1 ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism ; Heterogeneous-Nuclear Ribonucleoproteins/genetics ; Heterogeneous-Nuclear Ribonucleoproteins/metabolism ; Humans ; Mammals/genetics ; RNA Stability ; RNA, Messenger/metabolism
Chemical Substances	3' Untranslated Regions ; Heterogeneous Nuclear Ribonucleoprotein A1 ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B ; Heterogeneous-Nuclear Ribonucleoproteins ; RNA, Messenger
Language	English
Publishing date	2016-11
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1555-8584
ISSN (online)	1555-8584
DOI	10.1080/15476286.2016.1225645
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