While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple spatially separated nuclear domains including two types of transcription “hot zones.” Transcription hot zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.

The Qinghai-Tibetan Plateau (QTP) is the highest and one of the most extensive plateaus in the world. Phylogenetic, phylogeographic and ecological studies support plant diversifications on the QTP through multiple mechanisms such as allopatric speciation via geographic isolation, climatic oscillations and divergences, pollinator-mediated isolation, diploid hybridization and introgression, and allopolyploidy. These mechanisms have driven spectacular radiations and/or species diversifications in various groups of plants such as Pedicularis L., Saussurea DC., Rhododendron L., Primula L., Meconopsis Vig., Rhodiola L., and many lineages of gymnosperms. Nevertheless, much work is needed toward understanding the evolutionary mechanisms of plant diversifications on the QTP. Well-sampled biogeographic analyses of the QTP plants in the broad framework of the Northern Hemisphere as well as the Southern Hemisphere are still relatively few and should be encouraged in the next decade. This paper reviews recent evidence from phylogenetic and biogeographic studies in plants, in the context of rapid radiations, mechanisms of species diversifications on the QTP, and the biogeographic significance of the QTP in the broader context of both the Northern and Southern Hemisphere biogeography. Integrative multidimensional analyses of phylogeny, morphological innovations, geography, ecology, development, species interactions and diversifications, and geology are needed and should shed insights into the patterns of evolutionary assembly and radiations in this fascinating region.

Background: MicroRNAs (miRNAs) are small noncoding RNAs about 22 nt long that negatively regulate gene expression at the post-transcriptional level. Their key effects on various biological processes, e.g., embryonic development, cell division, differentiation and apoptosis, are widely recognized. Evidence suggests that aberrant expression of miRNAs may contribute to many types of human diseases, including cancer. Here we present a database of differentially expressed miRNAs in human cancers (dbDEMC), to explore aberrantly expressed miRNAs among different cancers. Results: We collected the miRNA expression profiles of 14 cancer types, curated from 48 microarray data sets in peer-reviewed publications. The Significance Analysis of Microarrays method was used to retrieve the miRNAs that have dramatically different expression levels in cancers when compared to normal tissues. This database provides statistical results for differentially expressed miRNAs in each data set. A total of 607 differentially expressed miRNAs (590 mature miRNAs and 17 precursor miRNAs) were obtained in the current version of dbDEMC. Furthermore, low-throughput data from the same literature were also included in the database for validation. An easy-to-use web interface was designed for users. Annotations about each miRNA can be queried through miRNA ID or miRBase accession numbers, or can be browsed by different cancer types. Conclusions: This database is expected to be a valuable source for identification of cancer-related miRNAs, thereby helping with the improvement of classification, diagnosis and treatment of human cancers. All the information is freely available through http://159.226.118.44/dbDEMC/index.html.

The human genome encodes thousands of long noncoding RNA (lncRNA) genes; the function of majority of them is poorly understood. Aberrant expression of a significant number of lncRNAs is observed in various diseases, including cancer. To gain insights into the role of lncRNAs in breast cancer progression, we performed genome-wide transcriptome analyses in an isogenic, triple negative breast cancer (TNBC/basal-like) progression cell lines using a 3D cell culture model. We identified significantly altered expression of 1853 lncRNAs, including ~500 natural antisense transcript (NATs) lncRNAs. A significant number of breast cancer-deregulated NATs displayed co-regulated expression with oncogenic and tumor suppressor protein-coding genes in cis. Further studies on one such NAT, PDCD4-AS1 lncRNA reveal that it positively regulates the expression and activity of the tumor suppressor PDCD4 in mammary epithelial cells. Both PDCD4-AS1 and PDCD4 show reduced expression in TNBC cell lines and in patients, and depletion of PDCD4-AS1 compromised the cellular levels and activity of PDCD4. Further, tumorigenic properties of PDCD4-AS1-depleted TNBC cells were rescued by exogenous expression of PDCD4, implying that PDCD4-AS1 acts upstream of PDCD4. Mechanistically, PDCD4-AS1 stabilizes PDCD4 RNA by forming RNA duplex and controls the interaction between PDCD4 RNA and RNA decay promoting factors such as HuR. Our studies demonstrate crucial roles played by NAT lncRNAs in regulating post-transcriptional gene expression of key oncogenic or tumor suppressor genes, thereby contributing to TNBC progression. Breast cancer is the most common cancer in women worldwide. The molecular mechanisms underlying the disease have been extensively studied, leading to dramatic improvements in diagnostic and prognostic approaches. Despite the overall improvements in survival rate, numerous cases of death by breast cancer are still reported per year, alerting us about the potential gap of knowledge in cancer molecular biology era. The emerging advances in new generation sequencing techniques have revealed that the majority of genome is transcribed into non-protein coding RNAs or ncRNAs, including thousands of long ncRNAs (lncRNAs) of unknown function. Natural antisense RNAs (NATs) constitute a group of lncRNAs that are transcribed in the opposite direction to a sense protein-coding or non-coding gene with partial or complete complementarity. In this manuscript, we investigate the role of NATs in breast cancer progression, focusing on the role of PDCD4-AS1, a NAT expressed from the established tumor suppressor PDCD4 gene locus. We observe that both PDCD4-AS1 and PDCD4 display concordant expression in breast cancer cell lines and patients. In mammary epithelial cells, PDCD4-AS1 promotes the stability of PDCD4 mRNA. PDCD4-AS1 by forming RNA duplex with PDCD4 RNA prevents the interaction between PDCD4 RNA and RNA decay factors in the nucleus.