Tsx Produces a Long Noncoding RNA and Has General Functions in the Germline, Stem Cells, and Brain

Anguera, Montserrat C.; Ma, Weiyuan; Clift, Danielle E.; Namekawa, Satoshi H.; Kelleher, Raymond J.; Lee, Jeannie T.

doi:10.1371/journal.pgen.1002248

Cited by 148 publications

(121 citation statements)

References 41 publications

(61 reference statements)

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“…The distal recombination breakpoint for RX2-derived male 830m (and 3695m) lies between DXPas28 and Exon 4 of Tsx (Table S1 and Table S2); therefore, Xite can be excluded but Tsx may still be part of this Xce candidate region. This is interesting because Tsx is reported to affect Tsix expression (Anguera et al 2011). In addition, the expression and transgenic analysis of the noncoding gene Linx, which is within the 830m X chromosome distal recombination breakpoint, suggests that Linx expression affects XCI choice and therefore Linx may also be a candidate for the Xce QTL ( Figure 5A) (Nora et al 2012).…”

Section: Discussionmentioning

confidence: 94%

Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome

et al. 2012

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During the development of female mammals, one of the two X chromosomes is inactivated, serving as a dosagecompensation mechanism to equalize the expression of X-linked genes in females and males. While the choice of which X chromosome to inactivate is normally random, X chromosome inactivation can be skewed in F1 hybrid mice, as determined by alleles at the X chromosome controlling element (Xce), a locus defined genetically by Cattanach over 40 years ago. Four Xce alleles have been defined in inbred mice in order of the tendency of the X chromosome to remain active: Xce a , Xce b , Xce c , Xce d . While the identity of the Xce locus remains unknown, previous efforts to map sequences responsible for the Xce effect in hybrid mice have localized the Xce to candidate regions that overlap the X chromosome inactivation center (Xic), which includes the Xist and Tsix genes. Here, we have intercrossed 129S1/SvImJ, which carries the Xce a allele, and Mus musculus castaneus EiJ, which carries the Xce c allele, to generate recombinant lines with single or double recombinant breakpoints near or within the Xce candidate region. In female progeny of 129S1/ SvImJ females mated to recombinant males, we have measured the X chromosome inactivation ratio using allele-specific expression assays of genes on the X chromosome. We have identified regions, both proximal and distal to Xist/Tsix, that contribute to the choice of which X chromosome to inactivate, indicating that multiple elements on the X chromosome contribute to the Xce. IN female mammals, either one of the two X chromosomes becomes inactivated during development of the embryo. This random form of X chromosome inactivation (XCI) was first proposed by Lyon (1961) to explain the mosaic pattern of X-linked phenotypes observed in coats of various mammals. XCI serves as a dosage-compensation mechanism to equalize the expression of most X-linked genes in females and males. The steps to random XCI during development of the embryonic lineage are thought to include counting of the number of X chromosomes and the choice of which will be active or inactive, followed by initiation, spreading and finally maintenance of the inactive state throughout development (Heard et al. 1997;Wutz 2011). While choice of which X to inactivate is known to be a primary event occurring early in development, when one X chromosome carries a detrimental mutation, preferential inactivation of the X chromosome with the mutation is typically observed (Morey and Avner 2010). This form of skewed XCI is exemplified in human cells and is most likely due to a secondary cell survival effect in choice (Puck and Willard 1998;Amos-Landgraf et al. 2006). In mice, random XCI is observed in homozygous females carrying X chromosomes from the same genetic background, whereas skewed XCI can be observed when females are heterozygous for X chromosomes from different backgrounds. In contrast to the situation observed in many human females, the process of this skewed XCI in mice is considered to be a primary event in t...

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Section: Discussionmentioning

confidence: 94%

Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome

et al. 2012

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“…Testis-specific X-linked (Tsx) was thought to be a proteincoding gene, but has recently been shown to be a lncRNA (Anguera et al 2011). The same group also found that Tsx is specifically expressed in pachytene spermatocytes, but not in spermatogonia or round spermatids, suggesting a regulatory role in germline meiotic division.…”

Section: Testis-specific X-linked (Tsx)mentioning

confidence: 99%

Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies

Luk¹,

Chan²,

Rennert³

et al. 2014

Reproduction

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Spermatogenesis is a complex developmental process in which undifferentiated spermatogonia are differentiated into spermatocytes and spermatids through two rounds of meiotic division and finally giving rise to mature spermatozoa (sperm). These processes involve many testis-or male germ cell-specific gene products that undergo strict developmental regulations. As a result, identifying critical, regulatory genes controlling spermatogenesis provide the clues not only to the regulatory mechanism of spermatogenesis at the molecular level, but also to the identification of candidate genes for infertility or contraceptives development. Despite the biological importance in male germ cell development, the underlying mechanisms of stage-specific gene regulation and cellular transition during spermatogenesis remain largely elusive. Previous genomic studies on transcriptome profiling were largely limited to protein-coding genes. Importantly, protein-coding genes only account for a small percentage of transcriptome; the majority are noncoding transcripts that do not translate into proteins. Although small noncoding RNAs (ncRNAs) such as microRNAs, siRNAs, and Piwi-interacting RNAs are extensively investigated in male germ cell development, the role of long ncRNAs (lncRNAs), commonly defined as ncRNAs longer than 200 bp, is relatively unexplored. Herein, we summarize recent transcriptome studies on spermatogenesis and show examples that a subset of noncoding transcript population, known as lncRNAs, constitutes a novel regulatory target in spermatogenesis.

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“…Plasticity lncRNAs are also implicated in modulating synapse formation and function. In particular, nuclear enriched abundant transcript 2 (NEAT2)/metastasis-associated lung adenocarcinoma transcript 1, brain cytoplasmic RNA 1, and testes-specific Xlinked are all lincRNAs that regulate synaptogenesis, local protein synthesis at the synapse, and fear-conditioning and short-term hippocampal memory consolidation, respectively [40][41][42]. Other lncRNAs are transcribed from genomic loci encompassing protein-coding genes involved in synapse development and functioning.…”

Section: Brain Developmentmentioning

confidence: 99%

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

2013

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The human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), a novel and important class of genes. Our knowledge of lncRNAs has grown exponentially since their discovery within the last decade. lncRNAs are expressed in a highly cell-and tissue-specific manner, and are particularly abundant within the nervous system. lncRNAs are subject to post-transcriptional processing and inter-and intra-cellular transport. lncRNAs act via a spectrum of molecular mechanisms leveraging their ability to engage in both sequence-specific and conformational interactions with diverse partners (DNA, RNA, and proteins). Because of their size, lncRNAs act in a modular fashion, bringing different macromolecules together within the three-dimensional context of the cell. lncRNAs thus coordinate the execution of transcriptional, post-transcriptional, and epigenetic processes and critical biological programs (growth and development, establishment of cell identity, and deployment of stress responses). Emerging data reveal that lncRNAs play vital roles in mediating the developmental complexity, cellular diversity, and activitydependent plasticity that are hallmarks of brain. Corresponding studies implicate these factors in brain aging and the pathophysiology of brain disorders, through evolving paradigms including the following: (i) genetic variation in lncRNA genes causes disease and influences susceptibility; (ii) epigenetic deregulation of lncRNAs genes is associated with disease; (iii) genomic context links lncRNA genes to disease genes and pathways; and (iv) lncRNAs are otherwise interconnected with known pathogenic mechanisms. Hence, Electronic supplementary material The online version of this article

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Tsx Produces a Long Noncoding RNA and Has General Functions in the Germline, Stem Cells, and Brain

Cited by 148 publications

References 41 publications

Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome

Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome

Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies

Long Non-coding RNAs: Novel Targets for Nervous System Disease Diagnosis and Therapy

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