DCL1

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Endoribonuclease Dicer homolog 1
Cartoon representation of Arabidopsis DCL1 in complex with pri-miRNA 166f (elucidated by Cryo-EM in Wei X. et al. Nat. Plants. 2021).gif
Cartoon representation of Arabidopsis DCL1 in complex with pri-miRNA 166f. Single chain of DCL1 in light purple catalyzing the cleavage of pri-miRNA-166f into pre-miRNA-166f, before one more cleavage step to finally release miRNA-166f.
Identifiers
Organism Arabidopsis thaliana
SymbolDCL1
Alt. symbolsAT1G01040
PDB 7ELD
UniProt Q9SP32
Other data
EC number EC:3.1.26
Chromosome 1: 0.02 - 0.03 Mb
Search for
Structures Swiss-model
Domains InterPro

DCL1 (an abbreviation of Dicer-like 1) is a gene in plants that codes for the DCL1 protein, a ribonuclease III enzyme involved in processing double-stranded RNA (dsRNA) and microRNA (miRNA). [1] Although DCL1, also called Endoribonuclease Dicer homolog 1, is named for its homology with the metazoan protein Dicer, its role in miRNA biogenesis is somewhat different, due to substantial differences in miRNA maturation processes between plants and animals, [2] as well due to additional downstream plant-specific pathways, where DCL1 paralogs like DCL4 participate, such Trans-acting siRNA biogenesis.

Contents

Function

DCL1 is localized exclusively in the plant cell nucleus, [3] together with the double-stranded RNA binding protein Hyponastic Leaves1 (HYL1), CTD-Phosphatase-Like1 (CPL1) and the zinc finger protein SERRATE (SE), form nuclear dicing bodies or D-bodies. In these membraneless organelles, pri-miRNAs are recognized and processes into pre-miRNAs and subsequently into mature miRNA duplexes, by the binding of additional proteins such as Constitutive Alterations in the Small RNAs Pathways9 (CARP9). [3] In plants, DCL1 is responsible both for processing a primary miRNA to a pre-miRNA, and for then processing the pre-miRNA to a mature miRNA. [4] [5] In animals, the equivalents of these two steps are carried out by different proteins; First, pri-miRNA processing takes place in the nucleus by the ribonuclease Drosha as part of the Microprocessor complex. Second and finally processing to a mature miRNA takes place in the cytoplasm by Dicer to yield a mature miRNA. [2]

PAZ domain plasticity

A model for DCL1-HYL-SE scaffolding for the pri-miRNA to pre-miRNA maturation process, as well for the pre-miRNA to miRNA maturation step helped by CARP9 binding into the DICER-Complex DCL1-HYL-SE-CARP9 scaffolding and miRNA maturation in plants.jpg
A model for DCL1-HYL-SE scaffolding for the pri-miRNA to pre-miRNA maturation process, as well for the pre-miRNA to miRNA maturation step helped by CARP9 binding into the DICER-Complex

In animals, hairpin-containing primary transcripts (pri-miRNAs) are cleaved by Drosha to generate precursor-miRNAs, a double strand palindromic structure typically call hairpin pre-miRNAs, which are subsequently cleaved by Dicer to generate mature miRNAs. Instead of being cleaved by two different enzymes, both cleavages in plants are performed by Dicer-like 1 (DCL1), despite a similar domain architecture between both homologous enzymes. [5] Recent single-particle cryo-electron microscopy structures of both complexes of dsRNA structures (pri-RNA and pre-miRNA) as ligand of Arabidopsis DCL1, in cleavage-competent state, suggest that PAZ domain plasticity allow its to get involved in pri-miRNA and pre-miRNA recognition, the possibility of an internal loop binding groove of this protein domain, which serves as an engine that transfers the substrate between two sequential cleavage events. [5]

Other dicer-like proteins

Although DCL1 is responsible for the majority of the miRNA processing in plants, most plants contain an additional set of DCLs proteins with related roles in RNA processing, [6] the number of additional members of the same family depends on the plant family. For instance, in Brassicaceae there are 5 additional paralog genes to DLC1, DCL2, DCL3, DCL4 and two RNASE III-LIKE genes RTL1 and RTL2; [7] [8] Howeversome dicots such as Populus trichocarpa [9] as well the majority of monocots plants have five to six DCLs, where DCL2 and DCL3 suffered an additional duplication into the genes DCL2a and DCL2. DCL3's duplication is monocot-specifict, generating the genes DCL3a and DCL3b, also called DCL3 and DCL5 respectively. [10] [7]

Related Research Articles

microRNA Small non-coding ribonucleic acid molecule

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then silence said mRNA molecules by one or more of the following processes:

  1. Cleavage of the mRNA strand into two pieces,
  2. Destabilization of the mRNA by shortening its poly(A) tail, or
  3. Reducing translation of the mRNA into proteins.
<span class="mw-page-title-main">Dicer</span> Enzyme that cleaves double-stranded RNA (dsRNA) into short dsRNA fragments

Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short double-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20–25 base pairs long with a two-base overhang on the 3′-end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component Argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).

The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).

<span class="mw-page-title-main">Argonaute</span> Protein that plays a role in RNA silencing process

The Argonaute protein family, first discovered for its evolutionarily conserved stem cell function, plays a central role in RNA silencing processes as essential components of the RNA-induced silencing complex (RISC). RISC is responsible for the gene silencing phenomenon known as RNA interference (RNAi). Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). Small RNAs guide Argonaute proteins to their specific targets through sequence complementarity, which then leads to mRNA cleavage, translation inhibition, and/or the initiation of mRNA decay.

<span class="mw-page-title-main">Drosha</span> Ribonuclease III enzyme

Drosha is a Class 2 ribonuclease III enzyme that in humans is encoded by the DROSHA gene. It is the primary nuclease that executes the initiation step of miRNA processing in the nucleus. It works closely with DGCR8 and in correlation with Dicer. It has been found significant in clinical knowledge for cancer prognosis and HIV-1 replication.

mir-30 microRNA precursor

miR-30 microRNA precursor is a small non-coding RNA that regulates gene expression. Animal microRNAs are transcribed as pri-miRNA of varying length which in turns are processed in the nucleus by Drosha into ~70 nucleotide stem-loop precursor called pre-miRNA and subsequently processed by the Dicer enzyme to give a mature ~22 nucleotide product. In this case the mature sequence comes from both the 3' (miR-30) and 5' (mir-97-6) arms of the precursor. The products are thought to have regulatory roles through complementarity to mRNA.

Trans-acting siRNA are a class of small interfering RNA (siRNA) that repress gene expression through post-transcriptional gene silencing in land plants. Precursor transcripts from TAS loci are polyadenylated and converted to double-stranded RNA, and are then processed into 21-nucleotide-long RNA duplexes with overhangs. These segments are incorporated into an RNA-induced silencing complex (RISC) and direct the sequence-specific cleavage of target mRNA. Ta-siRNAs are classified as siRNA because they arise from double-stranded RNA (dsRNA).

Mirtrons are a type of microRNAs that are located in the introns of the mRNA encoding host genes. These short hairpin introns formed via atypical miRNA biogenesis pathways. Mirtrons arise from the spliced-out introns and are known to function in gene expression.

<span class="mw-page-title-main">RNA interference</span> Biological process of gene regulation

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.

Degradome sequencing (Degradome-Seq), also referred to as parallel analysis of RNA ends (PARE), is a modified version of 5'-Rapid Amplification of cDNA Ends (RACE) using high-throughput, deep sequencing methods such as Illumina's SBS technology. The degradome encompasses the entire set of proteases that are expressed at a specific time in a given biological material, including tissues, cells, organisms, and biofluids. Thus, sequencing this degradome offers a method for studying and researching the process of RNA degradation. This process is used to identify and quantify RNA degradation products, or fragments, present in any given biological sample. This approach allows for the systematic identification of targets of RNA decay and provides insight into the dynamics of transcriptional and post-transcriptional gene regulation.

In molecular biology, small nucleolar RNA derived microRNAs are microRNAs (miRNA) derived from small nucleolar RNA (snoRNA). MicroRNAs are usually derived from precursors known as pre-miRNAs, these pre-miRNAs are recognised and cleaved from a pri-miRNA precursor by the Pasha and Drosha proteins. However some microRNAs, mirtrons, are known to be derived from introns via a different pathway which bypasses Pasha and Drosha. Some microRNAs are also known to be derived from small nucleolar RNA.

<span class="mw-page-title-main">MIR3648</span>

MicroRNA 3648 is a microRNA that in humans is produced by MIR3648 gene. This gene was recently shown to be specific to humans by Nathan H. Lents and colleagues.

MicroRNA 95 is a small non-coding RNA that in humans is encoded by the MIR95 gene.

<span class="mw-page-title-main">Microprocessor complex</span> Protein involved in processing RNA in animal cells

The microprocessor complex is a protein complex involved in the early stages of processing microRNA (miRNA) and RNA interference (RNAi) in animal cells. The complex is minimally composed of the ribonuclease enzyme Drosha and the dimeric RNA-binding protein DGCR8, and cleaves primary miRNA substrates to pre-miRNA in the cell nucleus. Microprocessor is also the smaller of the two multi-protein complexes that contain human Drosha.

mIR489 Non-coding RNA in the species Homo sapiens

MicroRNA 489 is a miRNA that in humans is encoded by the MIR489 gene.

<span class="mw-page-title-main">MicroRNA 499a</span> Non-coding RNA in the species Homo sapiens

MicroRNA 499a is a non-coding RNA that in humans is encoded by the MIR499A gene.

microRNA 203a

MicroRNA 203a is a small RNA that in humans is encoded by the preMIR203A gene.

<span class="mw-page-title-main">MIRLET7F2</span> Non-coding RNA in the species Homo sapiens

MicroRNA let-7f-2 is a protein that in humans is encoded by the MIRLET7F2 gene.

MicroRNA 517c is a protein that in humans is encoded by the MIR517C gene.

<span class="mw-page-title-main">DCL2</span> Dicer-like gene in plants

DCL2 is a gene in plants that codes for the DCL2 protein, a ribonuclease III enzyme involved in processing exogenous double-stranded RNA (dsRNA) into 22 nucleotide small interference RNAs (siRNAs).

References

  1. ↑ Schauer SE, Jacobsen SE, Meinke DW, Ray A (November 2002). "DICER-LIKE1: blind men and elephants in Arabidopsis development". Trends in Plant Science. 7 (11): 487–491. doi:10.1016/s1360-1385(02)02355-5. PMID   12417148.
  2. 1 2 Axtell MJ, Westholm JO, Lai EC (2011). "Vive la différence: biogenesis and evolution of microRNAs in plants and animals". Genome Biology. 12 (4): 221. doi: 10.1186/gb-2011-12-4-221 . PMC   3218855 . PMID   21554756.
  3. 1 2 3 Tomassi AH, Re DA, Romani F, Cambiagno DA, Gonzalo L, Moreno JE, et al. (September 2020). "The Intrinsically Disordered Protein CARP9 Bridges HYL1 to AGO1 in the Nucleus to Promote MicroRNA Activity". Plant Physiology. 184 (1): 316–329. doi:10.1104/pp.20.00258. PMC   7479909 . PMID   32636339.
  4. ↑ Fang X, Cui Y, Li Y, Qi Y (June 2015). "Transcription and processing of primary microRNAs are coupled by Elongator complex in Arabidopsis". Nature Plants. 1 (6): 15075. doi:10.1038/nplants.2015.75. PMID   27250010. S2CID   12544460.
  5. 1 2 3 Wei X, Ke H, Wen A, Gao B, Shi J, Feng Y (October 2021). "Structural basis of microRNA processing by Dicer-like 1". Nature Plants. 7 (10): 1389–1396. doi:10.1038/s41477-021-01000-1. PMID   34593993. S2CID   238240098.
  6. ↑ Parent JS, Bouteiller N, Elmayan T, Vaucheret H (January 2015). "Respective contributions of Arabidopsis DCL2 and DCL4 to RNA silencing". The Plant Journal. 81 (2): 223–232. doi:10.1111/tpj.12720. PMID   25376953.
  7. 1 2 Belal MA, Ezzat M, Zhang Y, Xu Z, Cao Y, Han Y (2022). "Integrative Analysis of the DICER-like (DCL) Genes From Peach (Prunus persica): A Critical Role in Response to Drought Stress". Frontiers in Ecology and Evolution. 10. doi: 10.3389/fevo.2022.923166 . ISSN   2296-701X.
  8. ↑ Nagano H, Fukudome A, Hiraguri A, Moriyama H, Fukuhara T (February 2014). "Distinct substrate specificities of Arabidopsis DCL3 and DCL4". Nucleic Acids Research. 42 (3): 1845–1856. doi:10.1093/nar/gkt1077. PMC   3919572 . PMID   24214956.
  9. ↑ Moura MO, Fausto AK, Fanelli A, Guedes FA, Silva TD, Romanel E, Vaslin MF (November 2019). "Genome-wide identification of the Dicer-like family in cotton and analysis of the DCL expression modulation in response to biotic stress in two contrasting commercial cultivars". BMC Plant Biology. 19 (1): 503. doi: 10.1186/s12870-019-2112-4 . PMC   6858778 . PMID   31729948.
  10. ↑ Chen S, Liu W, Naganuma M, Tomari Y, Iwakawa HO (May 2022). "Functional specialization of monocot DCL3 and DCL5 proteins through the evolution of the PAZ domain". Nucleic Acids Research. 50 (8): 4669–4684. doi:10.1093/nar/gkac223. PMC   9071481 . PMID   35380679.


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