This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
What is RNA interference?
RNA interference (RNAi) is a mechanism that inhibits gene expression during translation or hinders the transcription of specific genes (1). RNAi can also play a role in genome maintenance and development (1). RNAi include small interfering RNA (siRNA) which have complementary nucleotide sequence that target an mRNA strand. These siRNAs are unwound and guided by the protein RISC. RISC brings the siRNA to the matching mRNA sequence (1). This leads to the mRNA to being degraded inhibiting gene expression. The RNAi mechanism is explained more in depth in the YouTube video on the left (2). |
|
RNAi and FLNB in other organisms:
I went to RNAi database to start my RNAi search for FLNB. On this databases site, I checked "RNAi experiment" and imputed "FLNB" into the search box. By doing this, I discovered that no results matched with FLNB. Because of this, I went to Phenoback. On Phenobank, I entered "FLNB" for gene name and searched. Three results came up but two were for FLNA, a different filamin protein. One result was for FLNB, C23F12.2. Here you can see the genomic sequence RNA primers as well as look for phenotypic effects at early and late embryonic stages for experiments. For the FLNB gene no detectable defects resulted for wild types experiments. From Phenobank I was able to continue my search to Wormbase to look at RNA details. On Wormbase a product sequence appeared but there weren't any assay reaction conditions available.
A lack in RNAi information lead me to look at the role of FLNB in other organisms. I looked at several databases: Flybase, RGD, ZFIN, and TAIR with no luck. But I did find papers on the mouse model, though MGI showed no Larsen Syndrome model, and C. elegans using PubMed. Otherwise, not much research has been done on FLNB in many organisms that FLNB is present, found by homology.
A lack in RNAi information lead me to look at the role of FLNB in other organisms. I looked at several databases: Flybase, RGD, ZFIN, and TAIR with no luck. But I did find papers on the mouse model, though MGI showed no Larsen Syndrome model, and C. elegans using PubMed. Otherwise, not much research has been done on FLNB in many organisms that FLNB is present, found by homology.
flnb in mice is involved in very similar processes as in humans. One study knocked out flnb from the mouse model and found severe skeletal deformities in the mice that survive. Less than 3% of knock out mice for flnb survived to birth and most didn't live to 4 weeks (3). This proves that FLNB is very important for proper embryonic development.
|
FLN-1, the FLNB gene, in C. elegans has been studied, and is not involved in bone and cartilage development as in humans. In C. elegans FLN-1 is involved in brood size. Without FLN-1, C. elegans are lay damaged, unfertilized eggs (4).
|
Analysis:
There is a lack of information about FLNB RNAi from the several databases checked. This may be because there isn't any published research studies about FLNB in other model organisms except in the mouse and C. elegans. It would be good for research labs to look into FLNBs role in other organisms because FLNB is homologous to several species and well conserved in terms of percent identity and similarity. It was interesting to find that in C. elegans, a non-vertebrate, FLN-1 is involved in a different role than in vertebrates. It would be interesting to discover if FLNB has a different role in most non-vertebrate organisms, but sadly research hasn't been done.
References:
1.) "RNAi.gene-quantification.info: RNA interference (RNAi) basics and essential publication". Web. May 16, 2014. http://www.gene-quantification.de/rnai.html#def
2.) "NIH: RNAi". Web. May 16, 2014. http://www.ncats.nih.gov/research/reengineering/ncgc/rnai/rnai.html
3.) Zhou, X., et al., (2007). "Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development". PNAS, 104(10), doi: 10.1073/pnas.0608360104
4.) Kovacevic, I., Cram, EJ, (2010). "FLN-1/filamin is required for maintenance of actin and exit of fertilized oocytes from the spermatheca in C. elegans."Developmental Biology, 347(2), doi: 10.1016/j.ydbio.2010.08.005
2.) "NIH: RNAi". Web. May 16, 2014. http://www.ncats.nih.gov/research/reengineering/ncgc/rnai/rnai.html
3.) Zhou, X., et al., (2007). "Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development". PNAS, 104(10), doi: 10.1073/pnas.0608360104
4.) Kovacevic, I., Cram, EJ, (2010). "FLN-1/filamin is required for maintenance of actin and exit of fertilized oocytes from the spermatheca in C. elegans."Developmental Biology, 347(2), doi: 10.1016/j.ydbio.2010.08.005