Part 3 -2024-2.pdf

The nuclear lamina (a) Nuclear pores in the envelope 0.25 µm NUCLEOPLASM Inner membrane...

The nuclear lamina (a) Nuclear pores in the envelope 0.25 µm NUCLEOPLASM Inner membrane Nuclear of nuclear envelope pore complex 120 nm “Basket” of fibers Anchor protein Nuclear Numerous nuclear pores are lamina Ring graph of the nuclear envelope of subunit The fracture plane reveals faces he outer membrane. The arrows erinuclear space delimited by the Spoke Outer membrane Transporter of nuclear C). The NPC has an outer envelope built from about 30 different Fiber n electron micrographs, the ore complex is its octagonal Endoplasmic as the one in Figure 18-29a reticulum s arranged in an octagonal Ribosomes CYTOSOL ght subunits are seen to pro- c and nucleoplasmic sides of (b) Location of nuclear pores in nuclear membrane tral granules can be seen in FIGURE 18-29 Structure of the Nuclear Pore. (a) Negative omplexes in Figure 18-29a. staining of an oocyte nuclear envelope reveals the octagonal pattern re once thought to consist of the nuclear pore complexes. The arrow shows a central granule. through the pores, they are This nuclear envelope is from an oocyte of the newt Taricha granu- losa (TEM). (b) A nuclear pore is formed by fusion of the inner and Nuclear Lamina Meshwork of proteins lamins (Intermediate Filaments) Associated with the inner nuclear envelope Functions Structural support to nuclear envelope Genome organization Laminopathies Mutations affecting A-type lamins  Nuclear Lamina Provides Rigidity and Organization to the Nucleus Outer nuclear Inner nuclear membrane membrane Nuclear Lamin B Nuclear pore receptor Emerin pore LINC complexes Actin Intermediate Chromatin filament filament Microtubule Molecular Nuclear motor lamina Nucleus Different Adapter KASH domain nesprin Different Outer nuclear membrane proteins LINC Perinuclear space Different complexes SUN domain Inner nuclear membrane SUN Nuclear lamina proteins FIGURE 1851 The nuclear lamina is attached to chromatin and called LINC complexes, attach the lamins through the two nuclear through LINC complexes to the cytoskeleton. (a) Diagram ofth part of membranes to the cytoskeleton. (b) A LINC complex consists of a SUN Source: Molecular cell biology by Lodish et. al., 8 Edition a nucleus, showing the association of the lamin-containing nuclear lam- domain–containing protein that interacts with lamins and extends ina with chromatin and, through the two membranes of the nucleus, across the inner nuclear membrane, and a KASH domain–containing with the cytoskeleton. Proteins such as the membrane-associated protein that interacts with a SUN domain–containing protein in the lamin B receptor and emerin tether the lamin intermediate filaments to perinuclear space and crosses the outer nuclear membrane to interact the inner nuclear membrane. Lamins are also tethered to the nuclear with components of the cytoskeleton. See B. Burke and C. L. Stewart, membrane by the prenylation of lamin B (not shown). Diverse linkages, 2013, Nat. Rev. Mol. Cell Biol. 14:13. Nuclear Lamina Mitosis: Requires nuclear assembly and reassembly First Nuclear envelope turns into vesicles Disassembly by phosphorylation of lamins Second Vesicles fuse to reform nuclear envelope Assembly by dephosphorylation of lamins Ribonucleic acid (RNA) RNA Three main types: Messenger RNA (mRNA) copies DNA code Coding RNA Ribosomal RNA (rRNA) is an essential component of ribosomes Transfer RNA (tRNA) delivers amino acids to the protein being synthesized  FIGURE 18-30 M Transcription and RNA processing Chromosome replication port into and out of DNA eukaryotic cells store t in the nucleus but syn cytoplasm, all the prot rRNA mRNA tRNA nucleus must be trans cytoplasm (purple arr Ribosomal molecules and ribosom subunits protein synthesis in th transported outward f NUCLEUS arrows). The three kin required for protein sy RNA (rRNA), messen transfer RNA (tRNA). Proteins needed for transcription Ribosomal proteins Protein synthesis Proteins needed tRNA Growing for chromosome polypeptide replication Ribosome mRNA CYTOSOL Completed protein Source: Becker’s World of the Cell, 8th Ed., Chapter 18 Presumably, it is advantageous for a nucleus to possess a of about 5–6 subunits per minute pe barrier that keeps in the chromosomes and keeps out opposite direction is, if anything, organelles such as ribosomes, mitochondria, lysosomes, chromosomes are being replicated, h and microtubules. For example, the nuclear envelope pro- the rate of about 300,000 molecules RNA Interesting facts about DNA Eukaryotic cells have about 1000 times as much DNA as E. coli Yet eukaryotic cells encode only 5–10 times as many proteins as E. coli Excess, noncoding DNA “junk DNA” RNA Human genome ≈ 21,000 genes Actual fraction of protein-coding sequences 3% of genome1 2% of genome2 Approx. 75-80% of human genome is transcribed Produces ncRNA tRNA rRNA Hundred of thousands more 1. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. Landscape of transcription in human cells. Nature. 2012;489:101–108. 2. Gaudi S, Guffanti G, Fallon J, Macciardi F. J Comp Neurol. 2016 Oct 15;524(15):2944-54 RNA interference (RNAi) Small non-coding RNAs (sncRNAs) are used as guides to target mRNA transcripts or gene promoters. Small RNAs regulate transcription microRNA (miRNA) : about 22 bp small interfering RNA (siRNA): about 22 bp piwi-associated RNAs (piRNAs) RNA interference (RNAi) Process of RNA interference (RNAi) miRNA and siRNA are involved in this process may bind to mRNA and block translation may trigger mRNA degradation may inhibit transcription of a given gene important for the regulation of developmental, differentiation and cellular processes