Holy Quran guides us towards the Right Path

 

Science Research Ideas

Year 2004:

Biology:
“The mechanisms through which miRNAs regulate their target genes are largely unknown.” (He & Hannon, 2004)

We are left with the question of whether miRNAs are truly different from siRNAs or whether our current understanding fails to functionally distinguish these two species under physiological conditions.” (He & Hannon, 2004)

We must now begin to focus on the details that distinguish the modes of action of siRNAs and miRNAs in vivo to understand their true biological functions.” (He & Hannon, 2004)

Drosha is predominantly localized in the nucleus and contains two tandem RNase-III domains, a dsRNA binding domain and an amino-terminal segment of unknown function.” (He & Hannon, 2004)

Although the precise mechanisms that Drosha uses to discriminate miRNA precursors remain unknown, several studieshave addressed the features of pri-miRNAs that contribute to Drosha cleavage both in vitro and in vivo.” (He & Hannon, 2004)

Given our lack of knowledge about the precise structural elements that guide Dicer and Drosha cleavage, it is difficult to speculate about their exact biochemical mechanisms.However, it is probable that Drosha and Dicer share closely related mechanisms for the processing of miRNAs.” (He & Hannon, 2004)

Given our lack of knowledge about the precise structural elements that guide Dicer and Drosha cleavage, it is difficult to speculate about their exact biochemical mechanisms.However, it is probable that Drosha and Dicer share closely related mechanisms for the processing of miRNAs.” (He & Hannon, 2004)

The precise molecular mechanisms that underlie posttranscriptional repression by miRNAs still remain largely unknown.” (He & Hannon, 2004)

Despite progress in identifying protein and RNA components of the RISC (RNA- induced silencing complex), the biochemical mechanism by which this complex functions still remains unknown.” (He & Hannon, 2004)

In addition to AGO (Argaunote proteins) homologues, several other proteins have also been co-purified with the RISC. It is not clear, however, whether these RISC-associated proteins are core RISC components or whether they act as accessory proteins that provide functional specificity for the RISCs under different developmental and/or physiological contexts.” (He & Hannon, 2004)

The Mode of repression of lsy-6 (microRNA) is unknown. (He & Hannon, 2004)

 The target genes and the mode of repression of miR-14 (microRNA) is unknown. (He & Hannon, 2004)

The target genes and the mode of repression of miR-181 is unknown. (He & Hannon, 2004)

The function of miR-196 is unknown. (He & Hannon, 2004)

The function of miR-39 is unknown. (He & Hannon, 2004)

“The Burge group developed the TargetScan algorithm for predicting vertebrate miRNA targets on the basis of miRNAtarget complementarity (particularly at the 5region of the miRNA) and evolutionary conservation among vertebrates. In their first study, they experimentally validated 11 predicted targets out of 15 tested,using a HeLa cell reporter system that contains a luciferase reporter gene fused to the predicted target 32-UTR fragments.Among their predicted targets,29% have unknown functions,whereas 71% have diverse functions, such as DNA binding, transcriptional regulation, signaltransducer and kinase activity.Although the prediction success rate is difficult to determine on a genome-wide scale, these studies are an important step towards our understanding of miRNA function in animals.” (He & Hannon, 2004)

“Only a handful of miRNAs have been carefully studied so far, and the diverse expression patterns of miRNAs and altered miRNA expression under certain physiological conditions, such as tumorigenesis, indicate a range of unknown functions that might extend beyond developmental regulation.” (He & Hannon, 2004)

With relatively few exceptions, we know little about the precise roles of the vast majority of miRNAs in regulating gene expression. Furthermore, the precise mechanisms by which miRNA- and siRNA mediated repression might differ remain to be explained.” (He & Hannon, 2004)

References:
He, L., & Hannon, G. J. (2004). MicroRNAs: SMALL RNAs WITH A BIG ROLE IN GENE REGULATION. NATURE REVIEWS | GENETICS , 522-532.