Off Target Effects Dominate A Large Scale Rnai Screen For Modulators Of The Tgf B Pathway And Reveal Microrna Regulation Of Tgfbr2 Silence Full Text
Previous investigations and GenScript experiment data show that siRNA "off target" transcript silencing mediated by seed region sequence is widespreed "seed region" of siRNA is analogous to seed region of microRNA GenScript resourchers found that size of seed region plays a major part in off target prediction最も共有された！ √ seed region sirna Seed region sirna
Seed region sirna
Seed region sirna-Chemical modifications of 2'Omethyl (2'OMe) and locked nucleic acid (LNA) of the nucleotides in the seed region (positions 28) of the small interfering RNA (siRNA) guide strand significantly reduced seedmatched (SM) offtarget effects The siRNAThe nonseed region of siRNA was found to be subdivided into four domains, in which two nucleotide pairs (positions 13 and 14) were replaceable with cognate deoxyribonucleotides without reducing RNAi activity However, RNA sequences at positions 912 and 1518 were essential for effective gene silencing, and these two doublestranded RNA cores
Seed Sibling Controls For Rnai Hit Validation
SmartBase TM siRNA Recommended Modifications 1 Alternating 2'F bases and 2'OMe bases in siRNA enhances duplex stability and are more resistant to RNase degradation 2 Use a few 2'OMe bases in the seed region of the guide strand to decrease the Tm below 215 of this region 2'O methyl base hybridization with RNA has a lower TM 二 siRNA种子区引发脱靶效应 miRNA主要依靠种子区（seed region,指成熟体5'端 28个碱基）与靶基因的3'UTR区结合,抑制翻译。siRNA同miRNA产生机制类似（图3），也可通过种子区结合特征产生非靶抑制现象。 All tested shRNAs have a GCenriched central region and an AUenriched seed and 3′ region Sequences used in the seed and 3′ regions were indicated in the shRNA name Symbol before the underline represents the seed sequence
SiRNA that successfully targets the same gene18 An additional type of sequencedependent offtarget effect arises from the hexamer seed region, located at positions 2–7 of the siRNA sequence This region can bind to the 3′UTR of various mRNA species and can lead to a complex pattern of mRNA cleavage and translational siRNA recognition of the target mRNA is conferred by the "seed region", a six nucleotide stretch corresponding to positions 27 on the antisense siRNA strand After the siRNA seed region anneals, the catalytic RNase H domain of Argonaute then subjects perfectly complementary mRNA sequences 10 nucleotides from the 5' end of the incorporated siRNA Alternatively, siRNA could cause "partial offtarget" (seed matching offtarget) effects, in cases where the designed siRNA seeding region (second to seventh position) matches with 3′UTR of offtarget, affecting its translation This homology based offtarget could affect siRNA potency as they become unavailable to bind with the intended
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Although the seed region of siRNA is implicated in the miRNAlike offtarget effect, only some mRNAs, with this type of sequence complementarity, are silenced by siRNA By analogy, miRNAs regulate the expression of multiple mRNAs through binding of the seed region to the target 3′UTR, but not all mRNAs with the same degree of sequenceOur results confirm previous reports that strength of basepairing in the siRNA seed region is the primary factor determining the efficiency of offtarget silencing However, the degree of downregulation of offtarget transcripts with shared seed sequence is not necessarily similar, suggesting that there are additional auxiliary factors that influence the silencing potential
Incoming Term: seed region sirna,
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