Regulatory RNAs. Cells produce several types of RNA.
-
Upload
richard-sparks -
Category
Documents
-
view
220 -
download
0
Transcript of Regulatory RNAs. Cells produce several types of RNA.
![Page 1: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/1.jpg)
Regulatory RNAs
![Page 2: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/2.jpg)
Cells produce several types of RNA
![Page 3: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/3.jpg)
REGULATION BY RNAs IN BACTERIA
Activation and repression of translation by sRNAs (bacterial small RNAs)
![Page 4: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/4.jpg)
Ribo-switches reside within the transcripts of genes whose expression they control through changes in secondary structure
Organization of riboswitch RNAs
![Page 5: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/5.jpg)
The aptamer binds small molecules -> conformation changes -> conformation changes of expression platform -> termination of transcription or inhibition of translation initiation
Two examples of a SAM (S-Adenosylmethionine) sensing riboswitch
![Page 6: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/6.jpg)
Changes in secondary structure of a SAM-sensing riboswitch
![Page 7: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/7.jpg)
Riboswitches respond to a range of metabolites
![Page 8: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/8.jpg)
RNA INTERFERENCE IS A MAJOR REGULATORY MECHANISM IN EUKARYOTES
Short RNAs that silence genes are produced from a variety of sources and direct the silencing of genes in three different ways
RNA interference (RNA i)
Small interfering RNAs (siRNAs)
microRNAs (miRNAs)
RNA Inducing Silencing Complex (RISC)
![Page 9: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/9.jpg)
SYNTHESIS AND FUNCTION OF mi RNA MOLECULESmi RNAs have a characteristic structure that assists in identifying them and their target genes
Structure of some pre-miRNAs prior to processing to generate the mature miRNAs
![Page 10: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/10.jpg)
miRNAs are coded in both introns and exons in RNA
![Page 11: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/11.jpg)
An active miRNA is generated through a two-step nucleolytic processing
![Page 12: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/12.jpg)
Recognition and cleavage of pri-miRNA
![Page 13: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/13.jpg)
Dicer is the second RNA-cleavage enzyme involved in miRNA production
![Page 14: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/14.jpg)
Incorporation of a guide strand RNA into RISC makes the mature complex that is ready to silence gene expression
![Page 15: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/15.jpg)
Mature RISC
![Page 16: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/16.jpg)
Argonaute structure, showing RNA binding and RNase domain
![Page 17: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/17.jpg)
Si RNAs are regulatory RNAs generated from long double-stranded RNAs
![Page 18: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/18.jpg)
Small RNAs can transcriptionally silence genes by directing chromatin modification
RITS: RNA induced transcription silencing
![Page 19: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/19.jpg)
THE EVOLUTION AND EXPLOITATION OF RNAi
Did RNAi evolve as an immune system?
![Page 20: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/20.jpg)
RNAi has become a powerful tool for manipulating gene expression
sh RNA: short hairpin RNA genes (like miRNA)
![Page 21: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/21.jpg)
Dominant negative mutations created by RNA interference.
(A) Double-stranded RNA (dsRNA) can be introduced into C. elegans (1) by feeding the worms with E. coli expressing the dsRNA or (2) by injecting dsRNA directly into the gut. (B) Wild-type worm embryo. (C) Worm embryo in which a gene involved in cell division has been inactivated by RNAi. The embryo shows abnormal migration of the two unfused nuclei of the egg and sperm. (B, C, from P. Gönczy et al., Nature 408:331–336, 2000
![Page 22: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/22.jpg)
The Nobel Prize in Physiology or Medicine 2006"for their discovery of RNA interference - gene silencing by double-stranded RNA"
Andrew Z. Fire Craig C. Mello
1/2 of the prize 1/2 of the prize
USA USA
Stanford University School of Medicine Stanford, CA, USA
University of Massachusetts Medical School Worcester,
![Page 23: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/23.jpg)
REGULATORY RNAS AND X-INACTIVATION
X-inactivation creates mosaic individuals (calico cat)
![Page 24: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/24.jpg)
Chromosome wide alterations in chromatin structure can be inherited (dosage compensation)
X-inactivation
![Page 25: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/25.jpg)
Mammalian X-chromosome inactivation XIST: X-inactivationSpecific transcript
XIC: x-inactivationcenter
Xist is an RNA regulator that inactivates a single X chromosome in female mammals
![Page 26: Regulatory RNAs. Cells produce several types of RNA.](https://reader030.fdocuments.us/reader030/viewer/2022020117/56649e895503460f94b8db5f/html5/thumbnails/26.jpg)