Friday, April 25, 2008

Improved detection and annotation of transposable elements in sequenced genomes using multiple reference sequence sets.

Just a test~

Combining Flock (for blog post and RSS reader) and Connotea, you can get notice for the latest added reference and write blog after reading it, which is very COOL!!

View Original Article

Blogged with the Flock Browser

Wednesday, October 10, 2007

MiRNA learning note (1)

MicroRNA-143 and -145 in colon cancer. [DNA Cell Biol. 2007]
MicroRNAs (miRNAs) are endogenous, small non-coding RNAs (20-22 nucleotides) that negatively regulate gene expression at the translational level by base pairing to the 3' untranslated region of target messenger RNAs.
"It is predicted that 30% of protein-encoding genes are regulated by miRNAs."

Principles of microRNA regulation of a human cellular signaling network : Article : Molecular Systems Biology: "By analyzing the interactions between miRNAs and a human cellular signaling network, we found that miRNAs predominantly target positive regulatory motifs, highly connected scaffolds and most downstream network components such as signaling transcription factors, but less frequently target negative regulatory motifs, common components of basic cellular machines and most upstream network components such as ligands."

Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos -- Yu et al. 35 (1): 152 -- Nucle: "We found that the expression levels of miRNA targets are lower in all mouse and Drosophila tissues than in the embryos. We also found miRNAs more preferentially target ubiquitously expressed genes than tissue-specifically expressed genes. These results support the current suggestion that miRNAs are likely to be largely involved in embryo development and maintaining of tissue identity."

NB: This kind of expression survey at different ontogenetic stages is very important, because it covers a blind spot in analyses that depend on functional categories. For example GO analyses include categories for "development", but as Yu and colleagues point out, many genes change in expression during development that are not part of the "developmental" categories. (from John Hawks's weblog)

Identification of specific sequence motifs in the ...[Comput Biol Chem. 2007] - PubMed Result: "The significantly reduced frequency of occurrence of all 20 motifs in the regions 2000 bp upstream of 23,570 human RefSeq genes demonstrated that these motifs were specific to the upstream miRNA sequences. The most frequently observed motif M1 (GTGCTTMTAGTGCAG), with a MEME E-value of 3.8e-57 was distributed within 500 bp upstream of stem-loop sequences and was also miRNA-specific."

Regulatory circuit of human microRNA biogenesis. [PLoS Comput Biol. 2007] - PubMed Result: "Newly identified regulatory motifs occur frequently and in multiple copies upstream of miRNAs. The motifs are highly enriched in G and C nucleotides, in comparison with the nucleotide composition of miRNA upstream sequences. Although the motifs were predicted using sequences that are upstream of miRNAs, we find that 99% of the top-predicted motifs preferentially occur within the first 500 nucleotides upstream of the transcription start sites of protein-coding genes; the observed preference in location underscores the validity and importance of the motifs identified in this study. Our study also raises the possibility that a considerable number of well-characterized, disease-associated transcription factors (TFs) of protein-coding genes contribute to the abnormal miRNA expression in diseases such as cancer."

"Further analysis of predicted miRNA-protein interactions lead us to hypothesize that TFs that include c-Myb, NF-Y, Sp-1, MTF-1, and AP-2alpha are master-regulators of miRNA expression."

Spatial regulation of microRNA gene expression in the Drosophila embryo: "we investigate the possibility that localized expression is mediated by tissue-specific enhancers, comparable to those seen for protein-coding genes."

mir-309–6 polycistron (8-miR) : An 800-bp 5′ enhancer was identified that recapitulates this complex pattern when attached to a RNA polymerase II core promoter fused to a lacZ-reporter gene.

mir-1 gene: a mesoderm-specific enhancer located ≈5 kb 5′ of the miR-1 transcription unit.

Evidence is presented that the 8-miR enhancer is regulated by the localized Huckebein repressor, whereas miR-1 is activated by Dorsal and Twist. These results provide evidence that restricted activities of the 8-miR and miR-1 miRNAs are mediated by classical tissue-specific enhancers.

Monday, October 8, 2007

Purifying Selection Maintains Highly Conserved Noncoding Sequences in Drosophila -- Casillas et al. 24 (10): 2222 -- Molecular Biology and Evolution

Purifying Selection Maintains Highly Conserved Noncoding Sequences in Drosophila -- Casillas et al. 24 (10): 2222 -- Molecular Biology and Evolution: "We find that point mutations in intronic and intergenic CNSs exhibit a significant reduction in levels of divergence relative to levels of polymorphism, as well as a significant excess of rare derived alleles, compared with either the nonconserved spacer regions between CNSs or with 4-fold silent sites in coding regions"

TOADD: more about the methods.

//Long time, no reading~

Tuesday, September 11, 2007

assembly error or additional rearrangement?

1. Rearrangement Rate following the Whole-Genome Duplication in Teleosts -- Sémon and Wolfe 24 (3): 860 -- Molecular Biology and Evolution: "Rearrangement Rate following the Whole-Genome Duplication in Teleosts"

check out to see whether there is higher RR in zebrafish, theoretically.

2. ScienceDirect - Genomics : Phylogenetic analysis of three complete gap junction gene families reveals lineage-specific duplications and highly supported gene classes: "Note that in one of the zebrafish clusters the orientation of the two genes is inverted (cx41.8, cx44.1), suggesting an additional chromosomal rearrangement on the zebrafish chromosome."



3. Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis -- McEwen et al. 16 (4): 451 -- Genome Research: "In only two cases were all dCNE family members found to be located in the introns of paralogous genes (NBEA and LRBA) that were not the likely target genes. In these two specific cases the predicted target genes, MAB21L1 and MAB21L2, are also located in introns of NBEA and LRBA, respectively."

very interesting and important case! New paper in PLoS One, "Ancient Origin of the New Developmental Superfamily DANGER" also mentioned the Mab21L1/2. Check out!

Sunday, September 9, 2007

papers about fish evolution

1. The Evolutionary Fate and Consequences of Duplicate Genes, Science 10 November 2000:
http://www.sciencemag.org/cgi/content/full/290/5494/1151

2. Genome evolution and biodiversity in teleost fish, Heredity (2005) 94, 280–294.
http://www.nature.com/hdy/journal/v94/n3/full/6800635a.html

a review from J-N Volff

3. Functional Divergence of Two Zebrafish Midkine Growth Factors Following Fish-Specific Gene Duplication, Genome Res. 13:1067-1081, 2003
http://www.genome.org/cgi/content/full/13/6a/1067

Instance about "mdka and mdkb underwent functional divergence after duplication".

4. Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications, BMC Genomics 2007, 8:312
http://www.biomedcentral.com/1471-2164/8/312

new paper from Axel Meyer's group. Could be kind of explanation to GRB evolution.

Tuesday, August 7, 2007

new papers summary

New papers to read from the last week

1. Non-coding RNAs in Ciona intestinalis.
Bioinformatics. 2005 Sep 1;21 Suppl 2:ii77-8.
PMID: 16204130 [PubMed - in process]

2. Into the heart of darkness: large-scale clustering of human non-coding DNA.
Gill Bejerano1, David Haussler and Mathieu Blanchette
Bioinformatics.
2004 Aug 4;20 Suppl 1:i40-8.
PMID: 15262779 [PubMed - in process]

* I don't know why myNCBI sent me this paper until now. It's a paper in 2004. My Godsh~ But, it's def a good paper, which is obvious from the author list.

3. Exploiting conserved structure for faster annotation of non-coding RNAs without loss of accuracy.
Bioinformatics. 2004 Aug 4;20 Suppl 1:i334-41.
PMID: 15262817 [PubMed - in process]


4.
Regulation of the Gene Encoding GPR40, a Fatty Acid Receptor Expressed Selectively in Pancreatic beta Cells.
JBC
could be a story about subfunctionality by tissue/cell.

5. Ultraconserved non-coding sequence element controls a subset of spatiotemporal GLI3 expression.
Dev Growth Differ. 2007 Aug;49(6):543-53.
PMID: 17661744 [PubMed - in process]

6.
Dissecting the action of an evolutionary conserved non-coding region on renin promoter activity.
Nucleic Acids Res. 2007 Jul 26; [Epub ahead of print]
PMID: 17660193 [PubMed - as supplied by publisher]

Tuesday, July 31, 2007

learning note about ncRNA

  • siRNA and miRNA
Both are kinds of ncRNA(non-coding RNA);
Both are small, and short, ~20nt in length;
Both are involved in the RNA interference (RNAi) pathway where the siRNA interferes with the expression of a specific gene;
Difference in structure:
siRNA is a short (usually 21-nt) double-strand of RNA (dsRNA) with 2-nt 3' overhangs on either end.
while, miRNA is single-stranded RNA molecules of about 21-23 nucleotides in length with step-loop secondary structure.

Another essential differcence I guess is siRNA is exogenous, while miRNA is endogenous. So, when people use this techonology(I think siRNA is just kind of technology, not RNA in cell naturally like miRNA) to do RNAi, two issues (innate immunity, and off-targeting) are chanllenging us.
Direct transfection of an exogenous siRNA can be problematic, since the gene knockdown effect is only transient, particularly in rapidly dividing cells. One way of overcoming this challenge is to modify the siRNA in such a way as to allow it to be expressed by an appropriate vector, e.g. a plasmid. This is done by the introduction of a loop between the two strands (like a miRNA in form), thus producing a single transcript, which can be processed into a functional siRNA. People also use this way to avoid the non-specific effects by siRNA; converting siRNA into a miRNA. MicroRNAs occur naturally, and by harnessing this endogenous pathway it should be possible to achieve similar gene knockdown at comparatively low concentrations of resulting siRNAs. This should minimize non-specific effects.
  • about miRNA
miRNAs are first transcribed as part of a primary microRNA (pri-miRNA). This is then processed by the Drosha with the help of Pasha/DGCR8 (=Microprocessor complex) into pre-miRNAs. The ~75nt pre-miRNA is then exported to the cytoplasm by exportin-5, where it is then diced into 21-23nt siRNA-like molecules by Dicer. In some cases, multiple miRNAs can be found on the pri-miRNA.
It's hard to know how long and what's the original form of pri-miRNA on genome, since it's not stable after transcribed. Could be very long, ~several kb, connected with many stem-loop structure. (Is it possible to contain intron, either? I guess it's possible. And also alternative transcription, why not?)
pri-miRNA then is Drosha-proceeded into pre-miRNA. pre-miRNA is ~60-100nt long, hairpin structure (only one loop?) . Then it's exported outside to cytoplasm, where they are digested into a sequence-specific single-strand mature miRNA by Dicer.
The mature miRNA then binds to a complex called RNA-Induced Silencing Complex(RISC). The RISC-bound miRNA then binds to specific mRNA by significantly but not completely complementary to the mRNA.
The ways that miRNA inhibits gene expression are different in plant and animal. In plant, the formation of the double-stranded RNA(dsRNA) through the binding of the miRNA triggers the degradation of the mRNA transcript through a process similar to RNA interference (RNAi); while in animal, it prevents translation without causing the mRNA to be degraded. Animal miRNAs are usually (partially) complementary to a site in the 3' UTR whereas plant miRNAs are usually (highly) complementary to coding regions (also found in 5' UTR and 3' UTR) of mRNAs.